The U.S. is the largest maize producer in the world with a production of 300 million tons in 2012. Approximately 86% of the maize production is focused on the Midwestern states. The rest of the production is focused in the Southern states, where Texas is the largest maize producer. Grain yield in Texas ranges from 18 tons/ha in the irrigated production zones to 3 tons/ha in the dryland production zones. As a result, grain yield has increased slowly because of the poor production in the non-irrigated acres. Methods to improve the grain yield in Texas is to breed for maize varieties adapted to Texas growing conditions, including mapping genes that can be incorporated into germplasm through marker assisted selection. This dissertation includes two separate projects that exploit historical data and maize diversity to increase grain yield in Texas. For the first project, a large dataset collected by Texas AgriLife program was analyzed to elucidate past trends and future hints on how to improve maize yield within Texas. This study confirmed previous reports that the rate of increase for grain yield in Texas is less than the rate observed in the Midwestern US. For the second project, a candidate gene and whole genome association mapping analysis was performed for drought and aflatoxin resistance in maize. In order to do so, maize inbred lines from a diversity panel were testcrossed to isogenic versions of Tx714. The hybrids were evaluated under irrigated and non-irrigated conditions. The irrigated trials were inoculated with Aspergillus flavus and the aflatoxin level was quantified. This study found that the gene ZmLOX4 was associated with days to silk, and the gene ZmLOX5 gene was associated with plant and ear height. In addition, this study identified 13 QTL variants for grain yield, plant height, days to anthesis and days to silk. Furthermore, this study shows that diverse maize inbred lines can make hybrids that out yield commercial hybrids under heat and drought stress. Therefore, there are useful genes present in these diverse lines that can be exploited in maize breeding programs

Holistic and growth stage-specific screening is needed for identifying tolerant genotypes and for formulating strategies to mitigate the negative effects of abiotic stresses on crops. The objectives of this study were to characterize the genetic variability of 100 rice lines for early-season vigor, growth and physiological plasticity, and drought and temperature tolerance. Five studies were conducted to accomplish these objectives. In study 1 and 2, 100 rice genotypes consisting of several cultivars and experimental breeding lines were characterized for early-season vigor using several shoot and root morphological, physiological, and yield related traits. In study 3, low- and high-temperature tolerance assessed on select rice cultivars/hybrids during early-season. In study 4, genotypic variability in response to drought stress tolerance using morpo-physiological traits including roots was assessed under pot-culture conditions in a mini-greenhouse conditions. In study 5, the 100 rice genotypes were used to identify and validate SNP markers, and genome-wide association study (GWAS) to generate genotypic and phenotypic data with the objective of identifying new genetic loci controlling drought stress traits. Significant variability was recorded among rice genotypes and treatments for many traits measured. Early-season cumulative vigor response indices (CVRI) developed by summing individual responses indices for each trait varied among the rice genotypes, 21.36 (RU1404196) to 36.17 (N-22). Based on means and standard deviation of the CVRI, rice genotypes were classified as low- (43) and moderately low- (33), high- (16), and very high-vigor (5) groups. Total low-temperature response index values ranged from 18.48 to 23.15 whereas total high-temperature responses index values ranged from 42.01 to 48.82. Antonio, CLXL 745, and Mermentau were identified as sensitive to cold- and heat, and XL 753 was highly cold and heat tolerant genotypes tested. A cumulative drought stress response index (CDSRI) values varied between 14.7 (CHENIERE) and 27.9 (RU1402174) among the genotypes tested. This preliminary analysis of GWA indicated that substantial phenotypic and genotypic diversity exists in the 100 rice genotypes, despite their narrow genetic pool. The stress tolerant and high vigor rice genotypes will be valuable for rice breeders for developing new genotypes best suited under growing environments prone to early-season drought and temperature.

Cervical stenotic myelopathy (CSM) is an important musculoskeletal and neurologic disease of the horse. Clinical disease occurs due to malformations of the vertebrae in the neck causing stenosis of the cervical vertebral canal and subsequent spinal cord compression. The disease is multifactorial in nature, therefore a clearer understanding of the etiology and pathogenesis of CSM will allow for improved management and therapeutic practices. This thesis examines issues of equine CSM diagnosis, skeletal tissue pathology, and inherited genetic determinants utilizing advances in biomedical imaging technologies and equine genomics. Magnetic resonance imaging (MRI) data provided a more complete assessment of the cervical column through image acquisition in multiple planes. First, MRI was compared to standing cervical radiographs for detection of stenosis. Using canal area or the cord canal area ratio, MRI more accurately predicted sites of compression in CSM cases. Secondly, articular process skeletal pathology localized on MRI was found to be more frequent and severe in CSM horses compared to controls. In addition, lesions were generalized throughout the cervical column and not limited to the spinal cord compression sites. A subset of lesions identified on MRI was evaluated using micro-CT and histopathology. Osteochondrosis, osseous cyst-like structures, fibrous tissue replacement of bone, and osteosclerosis were observed. These lesions support likely developmental aberrations of vertebral bone and cartilage maturation with secondary biomechanical influences. Bone cyst-like structures are a novel finding in this disease. Finally, the long-standing question of the contribution of genetic determinants to CSM was investigated using a genome wide association study (GWAS). Multiple significant loci were identified supporting the influence of a complex genetic trait in clinical disease. A simple Mendelian trait controlled by one gene is unlikely given the detection of variants across multiple chromosomes. Major contributions from this research include documentation of articular process bone and cartilage pathology in horses with CSM, support for abnormal cervical vertebrae development being an important contributing factor in the etiology and/or pathogenesis of equine CSM, and evidence that multiple genetic loci contribute to the CSM disease phenotype.

No description available.

Rice (Oryza sativa) is the staple food for more than 3.5 billion people worldwide. As the population continues to grow, rice yield will need to increase by 1% every year for the next 30 years to keep up with the growth. In the US, Arkansas accounts for more than 50% of rice production. Over the last 68 years, rice production has continued to grow in Mississippi, placing it in fourth place after Arkansas, Louisiana, and California. Due to increasing rice acreage, regionally and worldwide, the need to develop abiotic stress-tolerant rice has increased. Unfortunately, current rice breeding programs lack genetic diversity, and many traits have been lost through the domestication of cultivated rice. Currently, stressors stemming from the continued effects of climate change continue to impact rice. To counteract the impacts of climate change, research has shifted to evaluating wild and weedy relatives of rice to improve breeding techniques. Weedy rice (Oryza sativa ssp.) is a genetically similar, noxious weed in rice with increased competitive ability. Studies have demonstrated that weedy rice has increased genetic variability and inherent tolerance to abiotic stressors. The aims of this study were to 1) screen a weedy rice mini-germplasm for tolerance to cold, heat, and complete submergence-stress, 2) utilize simple sequence repeat (SSR) markers and single nucleotide polymorphisms to evaluate the genetic diversity of the weedy rice population, and 3) use genome-wide association (GWAS) to identify SNPs associated with candidate genes within the population.

Made available in DSpace on 2016-06-02T20:21:37Z (GMT). No. of bitstreams: 1 6501.pdf: 1672444 bytes, checksum: 64754c3f12e26620a22bf55af9f8d5ff (MD5) Previous issue date: 2014-08-13 / The Brazilian cattle industry is presented as highlighted on the world stage and the significant participation of this productive sector in the economy means that there is concern with production losses, among which stands out those caused by infestation of Rhipicephalus (Boophilus) microplus, main ectoparasite vector cattle and various diseases. The genetic variability for resistance to the cattle tick shows that this trait can be genetically improved. For the execution of this work, it was used a study of genome wide association (GWAS) for resistance to Rhipicephalus (Boophilus) microplus, performed by Dr. Fernando Flores Cardoso, with 260 Hereford and 500 Braford animals. The monitoring of the infestation was accomplished by counting tick females larger than 4.5 mm from one of the animal's body side, and the degree of infestation was evaluated for each animal by averaging at least two consecutive counts, with intervals of approximately thirty days, in the months of highest incidence of the parasite. The animals were genotyped using a 50K SNP chip, and it was found a total of 37,346 SNPs that passed in quality test. Among these markers, 178 showed significant effects and allowed the mining of 175 genes in these regions, at an interval of 200 Kb (100 Kb for each side of each marker). Most of these polymorphisms associated with the trait is located in regions without defined functions (intronic and intergenic), and only one of them is located in the splicing region. The most significant regions of the GWAS were identified on chromosomes 7, 21 and 23, which were found 72 genes in linkage disequilibrium with the molecular markers. Therefore, a functional annotation of the genes on these 3 chromosomes was performed, allowing the choice of 11 candidate genes for the study of various metabolic pathways in which they are inserted. Among these pathways, the most important are those related to immune responses, secretion and intracellular transport, calcium influx and epidermal growth and differentiation. / A bovinocultura brasileira apresenta-se como destaque no cenário mundial e a expressiva participação deste setor produtivo na economia faz com que haja preocupação com as perdas produtivas, dentre as quais destaca-se aquelas causadas pela infestação do carrapato Rhipicephalus (Boophilus) microplus, principal ectoparasita de bovinos e vetor de diversas doenças. A variabilidade genética observada para a resistência dos bovinos ao carrapato permite que essa característica seja melhorada geneticamente, como forma alternativa de controle desses ectoparasitos. Para a execução do presente trabalho, foi utilizado um estudo de associação genômica ampla (GWAS) para a resistência ao carrapato R. microplus, o qual foi realizado pela equipe do Dr. Fernando Flores Cardoso (Embrapa Pecuária Sul), com 260 animais da raça Hereford e 500 animais da raça Braford. O monitoramento das infestações foi realizado por meio da contagem de fêmeas do carrapato com tamanho superior a 4,5 mm em um dos lados do corpo do animal, e o grau de infestação de cada animal foi avaliado pela média de pelo menos duas contagens consecutivas, com intervalos de aproximadamente trinta dias, conduzidas no sobreano, nos meses de maior incidência do parasito. Os animais foram genotipados com utilização de um chip de SNPs de 50 K e, após a realização do GWAS, verificou-se que um total de 37.346 SNPs passou nos teste de qualidade. Dentre esses marcadores, 178 SNPs apresentaram efeitos significativos e permitiram a mineração de 175 genes nessas regiões, em um intervalo de 200 Kb (100 Kb para cada lado de cada marcador). A maioria dos polimorfismos associados com a característica está localizada em regiões sem funções determinadas (intergênicas e intrônicas), apenas um deles encontra-se em região de splicing. Sendo assim, estes marcadores podem constituir mutações não causais que se encontram em desequilíbrio de ligação com mutações funcionais. As regiões mais significativas do GWAS foram identificadas nos cromossomos 7, 21 e 23, onde foram identificados 72 genes em desequilíbrio de ligação com os marcadores moleculares. Portanto, foi realizada uma anotação funcional dos genes localizados nesses 3 cromossomos, o que permitiu a seleção de 11 genes candidatos para um estudo mais aprofundado das vias metabólicas nas quais eles estão inseridos. Verificou-se que esses genes participam de processos importantes em vias já relacionadas com a resistência a carrapatos, tais como apresentação de antígenos, transporte e secreção intracelular e diferenciação da epiderme.

Cranberry common bean (Phaseolus vulgaris L.) is planted worldwide and consumed as a critical food source of human protein, fibre, carbohydrates, and minerals. Marsh spot (MS) is a physiogenic disorder which severely impacts seed quality in common beans. Previous studies indicate that MS involves a nutritional disorder caused by Mn deficiency. However, the inheritance and genetic mechanism of MS resistance are still not fully understood. To investigate the genetics of MS resistance, a population of 138 recombinant inbred lines (RILs) was developed from a bi-parental cross between a susceptible cultivar Messina and a resistant cultivar Cran09. The population and its two parents were evaluated for MS resistance during five consecutive years from 2015 to 2019 in both sandy and heavy clay soils in Morden, Manitoba, Canada. The severities of MS were rated and subsequently converted to MS resistance index (MSRI) and MS incidence (MSI). Statistical analyses indicated that MSI and MSRI were highly correlated (r = 0.96-0.99) and had high broad-sense heritability (H²) of 86.5% and 83.2%, respectively. Joint segregation analysis (JSA) of 18 phenotypic datasets from five years and two soil types showed that MS resistance was controlled by four major genes with genetic interactions - one of which may suppress the additive effect of the other three genes. To identify the quantitative trait loci (QTL) and the candidate genes associated with the MS resistance, the 138 RILs and the two parents were sequenced using genotyping by sequencing approach. A total of 52,676 SNPs were detected. After further filtering with a threshold of minor allele frequency > 0.01 and call rate > 20%, 2,061 SNPs were retained and then imputed for genetic map construction and QTL mapping. A genetic map consisting of 2,058 SNP markers on 11 linkage groups or chromosomes was constructed, which covered 1,004 recombination blocks with a total length of 6,449 cM and an average block of 6.42 cM. Three linkage map-based QTL-mapping models ICIM-ADD, ICIM-EPI, and GCIM and one genome-wide association study (GWAS) model RTM-GWAS for 18 phenotypic datasets from different years and soil types were used for identification of QTL. A total of 36 QTL, including 21 of additive and 15 of epistatic effects, were identified. Functional gene annotation analysis revealed 151 Mn-related candidate genes across the common bean reference genome and 17 of them harbored the six QTL discovered in this study. In conclusion, MS resistance in common bean is a highly heritable trait and controlled by several major and minor genes. The results of JSA and QTL mapping advance the current understanding of the genetic mechanisms of MS resistance in cranberry common bean, and provide additional resources for application in genomics-assisted breeding and potential isolation and functional characterization of the candidate genes.

Genome-wide association studies (GWASs) have reported numerous associations between risk variants and major psychiatric disorders (MPDs) including schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD) and others. We reviewed all of the published GWASs, and extracted the genome-wide significant (p<10) and replicated associations between risk SNPs and MPDs. We found the associations of 6 variants located in 6 genes, including L type voltage-gated calcium channel (LTCCs) subunit alpha1 C gene (), that were genome-wide significant ( ) and replicated at single-point level across at least two GWASs. Among them, the associations between MPDs and rs1006737 within are most robust. Thus, as a next step, the expression of the replicated risk genes in human hippocampus was analyzed. We found had significant mRNA expression in human hippocampus in two independent cohorts. Finally, we tried to elucidate the roles of venlafaxine and ω-3 PUFAs in the mRNA expression regulation of the replicated risk genes in hippocampus. We used cDNA chip-based microarray profiling to explore the transcriptome-wide mRNA expression regulation by ω-3 PUFAs (0.72/kg/d) and venlafaxine (0.25/kg/d) treatment in chronic mild stress (CMS) rats. ω-3 PUFAs and venlafaxine treatment elicited significant up-regulation. We concluded that might confer the genetic vulnerability to the shared depressive symptoms across MPDs and CACNA1C might be the therapeutic target for depressive endophenotype as well.

京都大学 / 新制・課程博士 / 博士(農学) / 甲第24654号 / 農博第2537号 / 新制||農||1097(附属図書館) / 学位論文||R5||N5435(農学部図書室) / 京都大学大学院農学研究科農学専攻 / (主査)教授 田尾 龍太郎, 教授 土井 元章, 准教授 中野 龍平 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

La Maladie Thrombo-Embolique Veineuse (MTEV) est une maladie dont les facteurs de risque sont à la fois environnementaux et génétiques. Les facteurs de risque génétiques bien établis sont les déficits en anti-thrombine, en protéine S, en protéine C, la mutation du Facteur V de Leiden (FVL), la mutation du Facteur (F) II G20210A, ainsi que le gène ABO dont les allèles A1 et B augmentent le risque de MTEV par rapport aux allèles A2 et O. Alors qu’une part importante de l’héritabilité de la MTEV reste inexpliquée, les études contemporaines se heurtent à un manque de puissance pour découvrir de nouveaux facteurs génétiques dont les effets sont de plus en plus faibles. En vue d’augmenter la puissance de détection de nouveaux gènes de susceptibilité à la MTEV, j’ai recherché les déterminismes génétiques de deux de ses phénotypes intermédiaires : les taux d’activité plasmatique du FVIII et les taux d’antigénémie de sa protéine de transport, le Facteur de von Willebrand (vWF). Dans un premier temps, j’ai réalisé une analyse de liaison des taux de FVIII et de vWF à partir d’un échantillon de cinq grandes familles franco-canadiennes (totalisant 255 personnes) recrutées via un cas de MTEV avec mutation FVL. Quatre régions liées aux taux de FVIII et/ou vWF ont été identifiées. L’une de ces régions correspondait au locus du gène ABO déjà connu pour influencer les taux de FVIII et vWF. La recherche de gènes candidats au sein des autres signaux de liaison s’est effectuée par l’étude in silico d’une analyse d’association pangénomique de la MTEV incluant 419 cas et 1228 témoins. Deux gènes candidats ont été identifiés : STAB2 et BAI3. J’ai ensuite réalisé des études d’associations de cinq polymorphismes de BAI3. L’un d’entre eux était d’une part associé à une élévation des taux de vWF (résultat obtenu dans un échantillon de 108 familles nucléaires en bonne santé et reproduit dans un échantillon de 916 patients non apparentés atteints de MTEV), et d’autre part associé au risque de survenue de MTEV parmi les sujets non porteurs de mutations FVL et FII de deux échantillons cas-témoins (respectivement 916 cas et 801 témoins, et 250 cas et 607 témoins). Quant à STAB2, durant le courant de ma thèse, deux de ces polymorphismes ont été décrits comme associés aux taux de FVIII et vWF au cours d’une vaste étude d’association pangénomique (GWAS) menée par le consortium CHARGE rassemblant 23 600 personnes. Dans un second temps, j’ai réalisé une méta-analyse de trois GWAS des taux de FVIII et vWF. Ces analyses avaient été conduites avec l’échantillon des cinq grandes familles franco-canadiennes et deux échantillons de 972 et 570 patients atteints de MTEV. Elles étaient ajustées sur les polymorphismes du gène ABO permettant de distinguer les allèles A1, A2, B et O, dans l’optique d’augmenter la puissance des analyses en diminuant la variance résiduelle des phénotypes. Aucun polymorphisme n’était associé ni aux taux de vWF ni à ceux de FVIII après prise en compte de la correction de Bonferroni pour tests multiples (p<10-7). Cependant, parmi les onze gènes qui présentaient des polymorphismes associés aux taux de vWF ou de FVIII avec une significativité p<10-5, de manière intéressante se trouvait STAB2. Cette étude a de plus permis de confirmer les associations nouvellement découvertes de polymorphismes situés dans les gènes VWF, STXBP5 et STX2. / The Venous Thromboembolism (VTE) risk factors are environmental and genetic. The well established risk factors are anti-thrombin, protein C, protein S deficiency, Factor V Leiden and factor II mutation and ABO gene, with A1 and B allele increasing the risk of VTE. While an important part of VTE heritability remains unexplained, contemporary studies fail to discover new susceptibility genes with weaker effects. In order to increase the discovery power, I searched for genetic geterminism of two intermediary phenotypes of VTE : Factor VIII plasmatic activity (FVIII) and von Willebrand factor antigenemia (vWF)First, I performed a linkage study of FVIII and vWF from a sample of 5 large pedigrees (N=255). Four loci have been identified. One included ABO gene. I searched for candidate genes located in the others loci by studying in silico results from o Genome Wide Association Study (GWAS) of the VTE including 419 cases and and 1228 controls. témoins. Two candidate genes were identified : STAB2 et BAI3. Then I performed association studies of five SNPs in BAI3 with FVIII and vWF. One of them was associated to vWF (in a sample of 108 nuclear families and 916 VTE patients), and associated to VTE in two case-controls samples (respectively 916 cases and 801 controls, and 250 cases et 607 controls).Second, I performed a meta-analysis of three GWAS of FVIII and vWF from the same 5 pedigrees and two samples of VTE (N=972 and 570) adjusted on ABO blood group. No polymorphisms were significant after Bonferoni correction (p<10-7). Nevertheless, among 11 genes carrying polymorphisms with a p<10-5, interestingly was STAB2. Futhermore, this study allowed to confirm newly discoverd association with VWF, STXBP5 et STX2.