Leveraging barrel medic genome sequence for the development and use of genomic resources for genetic analysis and breeding in legumes

BACKGROUND: A total of 62,591 cowpea expressed sequence tags (ESTs) were BLAST aligned to the whole-genome sequence of barrel medic (Medicago truncatula) to develop conserved intron scanning primers (CISPs). The efficacy of the primers was tested across 10 different legumes and on different varieties of cowpea, chickpea, and pigeon pea. Genetic diversity was assessed using the same primers on different cowpea genotypes. Singlenucleotide polymorphisms (SNPs) were detected, which were later converted to length polymorphism markers for easy genotyping. CISPs developed in this study were used in tagging resistance to bacterial leaf blight disease in cowpea. RESULTS: A total of 1262 CISPs were designed. The single-copy amplification success rates using these primers on 10 different legumes and on different varieties of cowpea, chickpea, and pigeon pea were approximately 60% in most of the legumes except soybean (47%) and peanut (37%). Genetic diversity analysis of 35 cowpea genotypes using 179 CISPs revealed 123 polymorphic markers with PIC values ranging from 0.05 to 0.59. Potential SNPs identified in cowpea, chickpea, and pigeon pea were converted to PCR primers of various sizes for easy genotyping. Using the markers developed in this study, a genetic linkage map was constructed with 11 linkage groups in cowpea. QTL mapping with 194 F3 progeny families derived from the cross C-152 × V-16 resulted in the identification of three QTLs for resistance to bacterial leaf blight disease. Conclusions: CISPs were proved to be efficient markers to identify various other marker classes like SNPs through comparative genomic studies in lesser studied crops and to aid in systematic sampling of the entire genome for well-distributed markers at low cost

Genome-Wide Analysis Reveals Four Novel Loci for Attention-Deficit Hyperactivity Disorder in Korean Youths

OBJECTIVES: The molecular mechanisms underlying attention-deficit hyperactivity disorder (ADHD) remain unclear. Therefore, this study aimed to identify the genetic susceptibility loci for ADHD in Korean children with ADHD. We performed a case-control and a family-based genome-wide association study (GWAS), as well as genome-wide quantitative trait locus (QTL) analyses, for two symptom traits. METHODS: A total of 135 subjects (71 cases and 64 controls), for the case-control analysis, and 54 subjects (27 probands and 27 unaffected siblings), for the family-based analysis, were included. RESULTS: The genome-wide QTL analysis identified four single nucleotide polymorphisms (SNPs) (rs7684645 near APELA, rs12538843 near YAE1D1 and POU6F2, rs11074258 near MCTP2, and rs34396552 near CIDEA) that were significantly associated with the number of inattention symptoms in ADHD. These SNPs showed possible association with ADHD in the family-based GWAS, and with hyperactivity-impulsivity in genome-wide QTL analyses. Moreover, association signals in the family-based QTL analysis for the number of inattention symptoms were clustered near genes IL10, IL19, SCL5A9, and SKINTL. CONCLUSION: We have identified four QTLs with genome-wide significance and several promising candidates that could potentially be associated with ADHD (CXCR4, UPF1, SETD5, NALCN-AS1, ERC1, SOX2-OT, FGFR2, ANO4, and TBL1XR1). Further replication studies with larger sample sizes are needed.

Genome-Wide Association Studies Associated with Backfat Thickness in Landrace and Yorkshire Pigs

Although pork quality traits are important commercially, genome-wide association studies (GWASs) have not well considered Landrace and Yorkshire pigs worldwide. Landrace and Yorkshire pigs are important pork-providing breeds. Although quantitative trait loci of pigs are well-developed, significant genes in GWASs of pigs in Korea must be studied. Through a GWAS using the PLINK program, study of the significant genes in Korean pigs was performed. We conducted a GWAS and surveyed the gene ontology (GO) terms associated with the backfat thickness (BF) trait of these pigs. We included the breed information (Yorkshire and Landrace pigs) as a covariate. The significant genes after false discovery rate (<0.01) correction were AFG1L, SCAI, RIMS1, and SPDEF. The major GO terms for the top 5% of genes were related to neuronal genes, cell morphogenesis and actin cytoskeleton organization. The neuronal genes were previously reported as being associated with backfat thickness. However, the genes in our results were novel, and they included ZNF280D, BAIAP2, LRTM2, GABRA5, PCDH15, HERC1, DTNBP1, SLIT2, TRAPPC9, NGFR, APBB2, RBPJ, and ABL2. These novel genes might have roles in important cellular and physiological functions related to BF accumulation. The genes related to cell morphogenesis were NOX4, MKLN1, ZNF280D, BAIAP2, DNAAF1, LRTM2, PCDH15, NGFR, RBPJ, MYH9, APBB2, DTNBP1, TRIM62, and SLIT2. The genes that belonged to actin cytoskeleton organization were MKLN1, BAIAP2, PCDH15, BCAS3, MYH9, DTNBP1, ABL2, ADD2, and SLIT2.

Investigation of Splicing Quantitative Trait Loci in Arabidopsis thaliana

The alteration of alternative splicing patterns has an effect on the quantification of functional proteins, leading to phenotype variation. The splicing quantitative trait locus (sQTL) is one of the main genetic elements affecting splicing patterns. Here, we report the results of genome-wide sQTLs across 141 strains of Arabidopsis thaliana with publicly available next generation sequencing datasets. As a result, we found 1,694 candidate sQTLs in Arabidopsis thaliana at a false discovery rate of 0.01. Furthermore, among the candidate sQTLs, we found 25 sQTLs that overlapped with the list of previously examined trait-associated single nucleotide polymorphisms (SNPs). In summary, this sQTL analysis provides new insight into genetic elements affecting alternative splicing patterns in Arabidopsis thaliana and the mechanism of previously reported trait-associated SNPs.

Genetic variants associated with fetal hemoglobin levels show the diverse ethnic origin in Colombian patients with sickle cell anemia / Las variantes genéticas asociadas con niveles de hemoglobina fetal señalan diversos orígenes étnicos en pacientes colombianos con anemia falciforme.

Introduction: Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies. Objective: We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia. Materials and methods: Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations. Results: We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population. Conclusion: These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease.

Introducción. La hemoglobina fetal es un importante factor modulador de la gravedad de la anemia falciforme, cuya expresión está muy condicionada por el factor genético. Los loci asociados con el incremento de la hemoglobina fetal pueden presentar frecuencias alélicas específicas para cada población. Objetivo. Investigar la presencia y el efecto de las variantes genéticas rs11886868, rs9399137, rs4895441 y rs7482144 asociadas con la persistencia de hemoglobina fetal, en 60 pacientes colombianos con anemia falciforme. Materiales y métodos. Se hizo la genotipificación de los polimorfismos de nucleótido simple ( Single Nucleotide Polymorphisms, SNP) mediante la técnica de polimorfismos de longitud de fragmentos de restricción ( Restriction Fragment Length Polymorphisms, RFLP) y el procedimiento TaqMan. La hemoglobina fetal (HbF) se cuantificó utilizando la técnica de desnaturalización alcalina de la oxihemoglobina. Las frecuencias genotípicas se compararon con las reportadas en poblaciones de referencia global. Resultados. Se observaron variantes genéticas ya reportadas para aumento de HbF en los cuatro SNP. La asociación genética entre los SNP y el incremento de la HbF no alcanzó significancia estadística. La frecuencia de estos alelos reflejó la siguiente composición específica en esta muestra de pacientes colombianos: una gran prevalencia de rs7482144-'A', lo que indica que el origen de la mutación para la anemia falciforme es África occidental, y una gran frecuencia de rs4895441-'G' y rs11886868-'C', lo que denota la influencia significativa del origen genético amerindio. Conclusión. Los resultados evidenciaron que la población con anemia falciforme de Colombia no tiene un único origen genético, sino que existen dos (africano y amerindio). Esta situación genética única ofrece la oportunidad de llevar a cabo un estudio más amplio de estos loci a nivel molecular. Se espera que el estudio de pacientes colombianos permita una visión diferente del efecto de los loci modificadores en esta enfermedad.

Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure / Reversão da Remodelação Cardíaca: um Marcador de Melhor Prognóstico na Insuficiência Cardíaca

In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis.

Na síndrome da insuficiência cardíaca, a disfunção do miocárdio gera um aumento da atividade neuro-hormonal, que é um mecanismo adaptativo e compensatório em resposta à redução do débito cardíaco. A atividade neuro-hormonal é estimulada inicialmente na tentativa de manter o paciente compensado, mas quando permanece aumentada, contribui para a intensificação das manifestações clínicas e do dano miocárdico. A remodelação cardíaca consiste nas alterações no volume do ventrículo bem como na espessura e forma da parede do miocárdio. Com o tratamento otimizado, pode ocorrer a reversão da remodelação, com melhora gradual da função cardíaca e consequente melhora do prognóstico.

Analysis of monotherapy prostate brachytherapy in patients with prostate cancer. Initial PSA and Gleason are important for recurrence?

Purpose To evaluate the clinical outcome of a cohort of localized prostate cancer patients treate with 125-I permanent brachytherapy at the São José Hospital – CHLC, Lisbon. Materials and Methods A retrospective analysis was carried out on 429 patients with low and intermediate-risk of prostate adenocarcinoma, according to the recommendations of the EORTC, who underwent 125I brachytherapies in intraoperative dosimetry “real-time” system between September 2003 and September 2013. Results The mean follow-up was 71.98 months. Biochemical relapse of disease by rising PSA (Phoenix criterion) was observed in 18 patients (4.2%). Through the application of Kaplan-Meier survival curves in this sample, the rate of survival at 6 years without biochemical relapse was higher than 95%. By Iog rank test comparing biochemical relapse with initial PSA (15-10 and <10) and Gleason values (7 and <7), there was no statistical difference (P=0.830) of the initial PSA in the probability of developing biochemical relapse. In relation to Gleason score, it was noted a statistical difference (P<0.05), demonstrating that patients with Gleason 7 are more likely to develop biochemical relapse. Conclusions Brachytherapy as monotherapy is at present an effective choice in the treatment of localized prostate adenocarcinoma. Biochemical relapses are minimal. The initial PSA showed no statistically difference in the rate of relapses, unlike the value Gleason, where it was demonstrated that patients with Gleason 7 have a higher probability of biochemical relapse. Cases with PSA bounce should be controlled before starting a salvage treatment. .

Identification of groundnut (Arachis hypogaea) SSR markers suitable for multiple resistance traits QTL mapping in African germplasm

Background This study aimed to identify and select informative Simple Sequence Repeat (SSR) markers that may be linked to resistance to important groundnut diseases such as Early Leaf Spot, Groundnut Rosette Disease, rust and aflatoxin contamination. To this end, 799 markers were screened across 16 farmer preferred and other cultivated African groundnut varieties that are routinely used in groundnut improvement, some with known resistance traits. Results The SSR markers amplified 817 loci and were graded on a scale of 1 to 4 according to successful amplification and ease of scoring of amplified alleles. Of these, 376 markers exhibited Polymorphic Information Content (PIC) values ranging from 0.06 to 0.86, with 1476 alleles detected at an average of 3.7 alleles per locus. The remaining 423 markers were either monomorphic or did not work well. The best performing polymorphic markers were subsequently used to construct a dissimilarity matrix that indicated the relatedness of the varieties in order to aid selection of appropriately diverse parents for groundnut improvement. The closest related varieties were MGV5 and ICGV-SM 90704 and most distant were Chalimbana and 47-10. The mean dissimilarity value was 0.51, ranging from 0.34 to 0.66. Discussion Of the 376 informative markers identified in this study, 139 (37%) have previously been mapped to the Arachis genome and can now be employed in Quantitative Trait Loci (QTL) mapping and the additional 237 markers identified can be used to improve the efficiency of introgression of resistance to multiple important biotic constraints into farmer-preferred varieties of Sub-Saharan Africa.

Strategies for elucidating functional significance of complex disease related loci / 中华预防医学杂志

Genome-wide association studies (GWAS) have identified thousands of genetic loci associated with complex diseases or traits. However, the exact biological functions of these loci are largely unknown. Recent functional annotation indicates that the majority of disease/trait associated loci are concentrated in regulatory DNA of human genome. Expression quantitative trait loci (eQTL) analyses, chromosome conformation capture related methods and genome editing methods (such as CRISPR/Cas9) may facilitate the functional study of these loci. Research on noncoding RNAs and rare variants may improve the functional understanding. These efforts may promise translation of GWAS findings to clinical practices.

Genetic Architecture of Transcription and Chromatin Regulation

DNA microarray and next-generation sequencing provide data that can be used for the genetic analysis of multiple quantitative traits such as gene expression levels, transcription factor binding profiles, and epigenetic signatures. In particular, chromatin opening is tightly coupled with gene transcription. To understand how these two processes are genetically regulated and associated with each other, we examined the changes of chromatin accessibility and gene expression in response to genetic variation by means of quantitative trait loci mapping. Regulatory patterns commonly observed in yeast and human across different technical platforms and experimental designs suggest a higher genetic complexity of transcription regulation in contrast to a more robust genetic architecture of chromatin regulation.

Pleiotropic effects of the sdw1 locus in barley populations representing different rounds of recombination

Background In the present study populations, representing different rounds of recombination were used for the analysis of phenotypic effects associated with the sdw1/denso locus. Other studies have mostly focused only on one type of population. Many different QTLs mapped at the same position as the sdw1/denso locus may indicate a pleiotropy of this gene or a tight linkage between genes conditioning quantitative traits. To date, results of studies have not unequivocally proven either of these two phenomena. Results Both breeding and molecular mapping experiments were undertaken to examine 200 single seed descent (SSD) and 60 doubled haploid (DH) lines obtained from the Maresi (with a semi-dwarfing gene) and Pomo cross combination. They were evaluated for the type of juvenile growth habit and certain agronomic traits were measured after harvesting. The estimates of mean values, standard errors and significance of effects were analyzed. In terms of the analyzed characteristics, the greatest variability was obtained for genotypes with the prostrate growth habit. Microsatellite markers (SSR) were also used to identify co-segregation with the sdw1/denso locus and Bmag0013, Bmag0877, Bmag0306b markers were linked the closest. A partial linkage map of chromosome 3H with the sdw1/denso semi-dwarfing gene was constructed and QTLs were identified. Conclusions Our experiments confirmed the impact of the semi-dwarfing gene on plant height, heading and flowering date both in SSD and DH populations, which may indicate pleiotropy. Moreover, a partial linkage between sdw1/denso locus and grain weight per spike and 1000-grain weight was found in the SSD population.

Genome-Wide Association Study of Metabolic Syndrome in Koreans

Metabolic syndrome (METS) is a disorder of energy utilization and storage and increases the risk of developing cardiovascular disease and diabetes. To identify the genetic risk factors of METS, we carried out a genome-wide association study (GWAS) for 2,657 cases and 5,917 controls in Korean populations. As a result, we could identify 2 single nucleotide polymorphisms (SNPs) with genome-wide significance level p-values (<5 x 10(-8)), 8 SNPs with genome-wide suggestive p-values (5 x 10(-8) < or = p < 1 x 10(-5)), and 2 SNPs of more functional variants with borderline p-values (5 x 10(-5) < or = p < 1 x 10(-4)). On the other hand, the multiple correction criteria of conventional GWASs exclude false-positive loci, but simultaneously, they discard many true-positive loci. To reconsider the discarded true-positive loci, we attempted to include the functional variants (nonsynonymous SNPs [nsSNPs] and expression quantitative trait loci [eQTL]) among the top 5,000 SNPs based on the proportion of phenotypic variance explained by genotypic variance. In total, 159 eQTLs and 18 nsSNPs were presented in the top 5,000 SNPs. Although they should be replicated in other independent populations, 6 eQTLs and 2 nsSNP loci were located in the molecular pathways of LPL, APOA5, and CHRM2, which were the significant or suggestive loci in the METS GWAS. Conclusively, our approach using the conventional GWAS, reconsidering functional variants and pathway-based interpretation, suggests a useful method to understand the GWAS results of complex traits and can be expanded in other genomewide association studies.

Numerical taxonomy of agronomic trait in cultivated Lonicera japonica / 中国中药杂志

Sixty-three morphological traits from 743 specimens of the 41 taxa within the cultivated Lonicera japonica were observed and measured, such as the height of plants, the length of leaf, the width of leaf, the length of anther, the alabastrum's number of one branch, the color of alabastrum and so on. A numerical taxonomy is presented by using the cluster analysis, principal components analysis (PCA) and factor analysis. Sixteen of 63 characters were screened by means of PCA and used for cluster analysis of 41 taxa with the method of Ward linkage and average euclidean distance. The cluster analysis showed that the 41 taxa could be divided into 5 groups when the Euclidean distance coefficient was 11.84. The factor analysis indicated that the shape of leaf, color of alabastrum, the pilosity and color of twiggery were of significance for the cultivated L. japonica classification. The results of this study will be a base for the core collection and breeding of L. japonica.

Comparison of agronomic traits of Panax notoginseng between traditional cultivated fields and new cultivated fields / 中国中药杂志

<p><b>OBJECTIVE</b>In order to provide scientific basis for introduction breeding and production regionalization of Panax notoginseng, the environment of producing area, agronomic traits and medicinal material output were investigated.</p><p><b>METHOD</b>Using field survey sampling at harvest time, agronomic traits indicators of leaf segment, stem segment and roots segment etc. of commodity P. notoginseng, longitude and latitude, elevation, soil type, landform of producing area were measured and observed.</p><p><b>RESULT</b>The P. notogiseng cultivation was expanding from traditional area like Wenshang to new areas as Honghe, Kunming, Qujing at large scale. Comparing with traditional cultivated fields, the elevation of new fields, which are red soil of moderate or low mountain slopes and gentle hills between 1 800-2 130 m, increases markedly. The agronomic traits of new cultivated fields such as plant height, stem diameter, the ground and underground biomass were better than those of traditional cultivated fields in varying degree. Furthermore, the root weight, taproot weight, taproot length and other agronomic index augmented more than 20%. Comparison among different cultivated fields showed P. notoginseng of Honghe Shiping Niujie, Kunming Shilin Guishan, Honghe Jiangshui Guanting etc. had better agronomic traits, the plant were thick and tall, the taproot and the top of reed were large, the number of root was more. Inversely, P. notoginseng of Kunming Guandu Xiaoshao, Guangxi Jingxi Lutong, Wenshang Yanshan Jiangna were thin and small. Cluster analysis showed that cultivated fields of P. notoginseng which was across clustered by traditional and new cultivated fields can be divided into three groups, including a high-yielding region insist of three new cultivated fields Honghe Shiping Niujie, Kunming Shilin Guishan, Honghe Jiangshui Guanting and one traditional cultivated field Wenshan Yanshan Jiangna. Correlation analysis indicated that the size and weight of taproot and top of reed were significantly positive correlated with plant height, stem diameter, leaf size, leaf weight and stem weight. Regression analysis pointed out that stem diameter, leaf width, leaf length/width, leaf weight were the main factors affecting the dry weight of taproot, and the main factors influencing the dry weight of top of reed were plant height, petiole, leaf length, leaf width and other agronomic traits.</p><p><b>CONCLUSION</b>From agronomic traits, P. notoginseng in new cultivated fields were more robust than that in traditional fields, but besides the length of taproot, the difference of rest agronomic traits didn't reach the significant level. It is suggested that, in the west and the north of traditional area, the red soil land of moderate or low mountain slopes and gentle hills where the elevation is between 1 800-2 130 m is suitable for cultivating P. notoginseng. Honghe Shiping Niujie, Honghe Jianshui Guanting, Kuming Shilin Gongshan can be used as vital development area for commodity P. notoginseng.</p>

Field experiment of F1 generation and superior families selection of Dendrobium officinale / 中国中药杂志

Based on randomized block design of experiment, agronomic traits and yields of 14 F1 generations of Dendrobium officinale were determined. The results showed that the differences in agronomic traits and yields among families were significant, and the hybrid vigor was obvious. Families of 6b x 2a, 9 x 66 and 78 x 69 were selected with the remarkable superiority of yields, agronomic traits and product customization. Correlation analysis between agronomic traits and yields showed that plant height, stem diameter, leaf number, blade length and blade width were all significantly correlated with biological yields and economic yields. Among which, stem diameter, leaf number and blade length were the most significant, and an optimal linear regression model could be established. When the number of shoots was fewer than 4.5, both biological yields and economic yields increased with the increasing number of shoots, but it could not much affect yields when the number of shoots was larger than 4.5. Shoots number, stem diameter and leaf index were basic stability when compared biennial traits to annual, which could be used for early selection.

Caracterização molecular da resistência a inseticidas químicos em populações de Aedes aegypti / Molecular characterization of chemical insecticide resistance in Aedes aegypti

A resistência a inseticidas químicos representa uma das maiores limitações em programas de controle de insetos. Dentre os diferentes mecanismos que levam o inseto à resistência, os principais são as alterações do sítio-alvo e a via metabólica. Essa última é representada por enzimas de detoxificação, como esterases, glutationas S-tranferases e oxidases. Mais de 200 genes de detoxificação foram identificados em Ae. aegypti, o que torna complexa a identificação mutações pontuais envolvidas neste mecanismo. Sendo assim, o presente estudo teve como objetivo identificar e caracterizar genes envolvidos na resistência a inseticidas em Ae. aegypti. Para o mapeamento de loci de herança quantitativa (QTL), microssatélites foram utilizados para genotipar indivíduos das gerações F0 e F2, provenientes dos cruzamentos entre a linhagem resistente ao temephos RecR, e as susceptíveis Red e MoyoD. Um QTL foi mapeada no cromossomo II, respondendo a aproximadamente 97 por cento da variação da resistência ao temephos. Diferentes genes de esterase foram identificados na região de QTL, demonstrando o envolvimento de outros genes de resistência na RecR, além daqueles identificados em trabalho prévio, com um chip de microarranjos. O presente trabalho estudou a região 5' UTR do gene da oxidase CYP6N12, identificado previamente como superexpresso na linhagem RecR. A análise da região revelou na RecR a presença de um alelo (R), com 14 pb a mais, que encontrava-se associado com a resistência ao temephos (fR= 0,625). Enquanto que, o mesmo alelo foi encontrado em menor frequência na RecRev (fR = 0,12). A presença desse alelo induziu a uma expressão do gene em 10 vezes na RecR e 4 vezes na RecRev. O sequenciamento de parte do gene da acetilcolinesterase de mosquitos da RecR e da linhagem susceptível Rockefeller, demonstrou a ausência de mutações nas duas colônia. Por fim, mutações no gene do canal de sódio foram avaliadas em populações de Ae. aegypti do Ceará, resistentes à cipermetrina. A mutação Ile1011Met foi encontrada em associação com a resistência em indivíduos do Crato, enquanto que o alelo mutante 1016Ile foi detectado pela primeira vez no Crato e Juazeiro do Norte. A identificação e mapeamento dos genes de resistência a inseticidas químicos em Ae. aegypti poderão contribuir para o desenvolvimento de novos métodos de diagnóstico e manejo da resistência.

Combined Genome-Wide Linkage and Association Analyses of Fasting Glucose Level in Healthy Twins and Families of Korea

This study was undertaken to identify genetic polymorphisms that are associated with the risk of an elevated fasting glucose (FG) level using genome-wide analyses. We explored a quantitative trait locus (QTL) for FG level in a genome-wide study from a Korean twin-family cohort (the Healthy Twin Study) using a combined linkage and family-based association analysis approach. We investigated 1,754 individuals, which included 432 families and 219 pairs of monozygotic twins. Regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2, were found to show evidence of linkage with FG level, and several markers in these regions were found to be significantly associated with FG level using family-based or general association tests. In particular, a single-nucleotide polymorphism (rs6138953) on the PTPRA gene in the 20p13 region (combined P = 1.8 x 10(-6)) was found to be associated with FG level, and the PRKCB1 gene (in 16p12.1) to be possibly associated with FG level. In conclusion, multiple regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2 are associated with FG level in our Korean twin-family cohort. The combined approach of genome-wide linkage and family-based association analysis is useful to identify novel or known genetic regions concerning FG level in a family cohort study.

Genome-wide association study with memory measures as a quantitative trait locus for schizophrenia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between gene polymorphisms and memory function through a genome-wide association study (GWAS) of schizophrenia and control group. Memory cognition was used as a quantitative trait (QT).</p><p><b>METHODS</b>Ninty-eight subjects with chronic schizophrenia and 60 matched controls were genotyped with HumanHap660 Bead Array. The results were correlated with quantitative traits including memory and memory delay.</p><p><b>RESULTS</b>Five candidate genes, including RASGRF2 (rs401758, P = 8.03×10(-5)), PLCG2 (rs7185362, P= 4.54×10(-5)), LMO1 (rs484161, P=9.80×10(-7), CSMD1 (rs2469383, P= 2.77×10(-6)) and PRKG1 (rs7898516, P=6.94×10(-5)) were associated with memory cognition deficits.</p><p><b>CONCLUSION</b>Using memory cognition as a quantitative trait, this Genome- wide association study has identified 5 susceptibility loci. With their association with nervous system development, neuronal growth, axon guidance and plasticity, brain development, above loci may play a role in the development of memory dysfunction in schizophrenia.</p>

Understanding Disease Susceptibility through Population Genomics

Genetic epidemiology studies have established that the natural variation of gene expression profiles is heritable and has genetic bases. A number of proximal and remote DNA variations, known as expression quantitative trait loci (eQTLs), that are associated with the expression phenotypes have been identified, first in Epstein-Barr virus-transformed lymphoblastoid cell lines and later expanded to other cell and tissue types. Integration of the eQTL information and the network analysis of transcription modules may lead to a better understanding of gene expression regulation. As these network modules have relevance to biological or disease pathways, these findings may be useful in predicting disease susceptibility.

QTL mapping for physiology, yield and plant architecture traits in cotton (Gossypium hirsutum L. ) grown under well-watered versus water-stress conditions

Increasing scarcity of irrigation water is a major threat to sustainable production of cotton (Gossypium hirsutum L.). Identifying genomic regions contributing to abiotic stress tolerance will help develop cotton cultivars suitable for water-limited regions through molecular marker-assisted breeding. A molecular mapping F2 population was derived from an intraspecific cross of the drought sensitive G. hirsutum cv. FH-901 and drought tolerant G. hirsutum cv. RH-510. Field data were recorded on physiological traits (osmotic potential and osmotic adjustment); yield and its component traits (seedcotton yield, number of bolls/plant and boll weight); and plant architecture traits (plant height and number of nodes per plant) for F2, F2:3 and F2:4 generations under well-watered versus water-limited growth conditions. The two parents were surveyed for polymorphism using 6500 SSR primer pairs. Joinmap3.0 software was used to construct linkage map with 64 polymorphic markers and it resulted into 35 markers mapped on 12 linkage groups. QTL analysis was performed by composite interval mapping (CIM) using QTL Cartographer2.5 software. In total, 7 QTLs (osmotic potential 2, osmotic adjustment 1, seedcotton yield 1, number of bolls/plant 1, boll weight 1 and plant height 1) were identified. There were three QTLs (qtlOP-2, qtlOA-1, and qtlPH-1) detected only in water-limited conditions. Two QTLs (qtlSC-1 and qtlBW-1) were detected for relative values. Two QTLs (qtlOP-1 and qtlBN-1) were detected for well-watered treatment. Significant QTLs detected in this study can be employed in MAS for molecular breeding programs aiming at developing drought tolerant cotton cultivars.