Obesity, diabetes, hypertension, and heart disease are highly heritable conditions that in aggregate are the major causes of morbidity and mortality in the developed world and are growing problems in developing countries. To map the causal genes, we conducted a population screen for these conditions on the Pacific Island of Kosrae. Family history and genetic data were used to construct a pedigree for the island. Analysis of the pedigree showed highly significant heritability for the metabolic traits under study. DNA samples from 2,188 participants were genotyped with 405 microsatellite markers with an average intermarker distance of 11 cM. A protocol using LOKI, a Markov chain Monte Carlo sampling method, was developed to analyze the Kosraen pedigree for height, a model quantitative trait. Robust quantitative trait loci for height were found on 10q21 and 1p31. This protocol was used to map a set of metabolic traits, including plasma leptin to chromosome region 5q35; systolic blood pressure to 20p12; total cholesterol to 19p13, 12q24, and 16qter; hip circumference to 10q25 and 4q23; body mass index to 18p11 and 20q13; apolipoprotein B to 2p24-25; weight to 18q21; and fasting blood sugar to 1q31-1q43. Several of these same chromosomal regions have been identified in previous studies validating the use of LOKI. These studies add information about the genetics of the metabolic syndrome and establish an analytical approach for linkage analysis of complex pedigrees. These results also lay the foundation for whole genome scans with dense sets of SNPs aimed to identifying causal genes.

Master of Science / Department of Biology / Theodore J. Morgan / The organismal response to temperature represents one of the most ubiquitous processes that occur in the natural world, and this response is critical for survival in most habitats. Increased attention should be focused on how organisms cope with temperature extremes, either through adaptation, plasticity, or a combination of both, as climate models predict increased variations in temperature accompanied by novel thermal extremes. Drosophila melanogaster is an excellent resource for answering questions pertaining to how organisms persist in environmental extremes because they originated in central tropical Africa and have since colonized nearly the entire globe, exposing them to many novel thermal stressors. In this work I elucidated regions of the genome contributing to phenotypic variation in cold tolerance and thermal plasticity. A quantitative trait locus (QTL) approach was used, which involved phenotyping roughly 400 recombinant inbred lines (RILs) of D. melanogaster from the Drosophila Synthetic Population Resource (DSPR). The DSPR captures genetic variation from around the globe, allowing for precision mapping of cold tolerance and thermal plasticity QTL, while simultaneously determining the frequency of the QTL alleles. Upon development at both 18°C and 25°C, RILS were measured for a common cold tolerance metric, chill-coma recovery time (CCR), and a plasticity value was derived as the change in CCR between environments. Analysis of variance revealed significant effects of sex, line (RIL), treatment (temperature), and line by treatment interaction (GxE). Mapped QTL for chill-coma recovery time at 18°C and 25°C spanned the same regions as several studies previously reported, validating the automated phenotyping method used and the mapping power of the DSPR. QTL between CCR at 18°C and 25°C overlapped significantly, and QTL for thermal plasticity shared the similar regions as QTL for CCR, but also exhibited two non-overlapping QTL on the left arm of the third chromosome. This study demonstrated the tremendous amount of variation present in cold tolerance phenotypes and identified candidate regions of the genome that contribute to thermal plasticity and require further investigation.

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Doctor of Philosophy / Department of Agronomy / Guihua Bai / Allan K. Fritz / Wheat pre-harvest sprouting (PHS), germination of physiologically matured grains in a wheat spike before harvesting, can cause significant reduction in grain yield and end-use quality. Many quantitative trait loci (QTL) for PHS resistance have been reported in different sources. To determine the genetic architecture of PHS resistance and its relationship with grain color (GC) in US hard winter wheat, a genome-wide association study (GWAS) on both PHS resistance and GC was conducted using in a panel of 185 U.S. elite breeding lines and cultivars and 90K wheat SNP arrrays. PHS resistance was assessed by evaluating sprouting rates in wheat spikes harvested from both greenhouse and field experiments. Thirteen QTLs for PHS resistance were identified on 11 chromosomes in at least two experiments, and the effects of these QTLs varied among different environments. The common QTLs for PHS resistance and GC were identified on the long arms of the chromosome 3A and 3D, indicating pleiotropic effect of the two QTLs. Significant QTLs were also detected on chromosome arms 3AS and 4AL, which were not related to GC, suggesting that it is possible to improve PHS resistance in white wheat. To identify markers closely linked to the 4AL QTL, genotyping-by-sequencing (GBS) technology was used to analyze a population of recombinant inbred lines (RILs) developed from a cross between two parents, “Tutoumai A” and “Siyang 936”, contrasting in 4AL QTL. Several closely linked GBS SNP markers to the 4AL QTL were identified and some of them were coverted to KASP for marker-assisted breeding. To investigate effects of the two non-GC related QTLs on 3AS and 4AL, both QTLs were transferered from “Tutoumai A” and “AUS1408” into a susceptible US hard winter wheat breeding line, NW97S186, through marker-assisted backcrossing using the gene marker TaPHS1 for 3AS QTL and a tightly linked KASP marker we developed for 4AL QTL. The 3AS QTL (TaPHS1) significantly interacted with environments and genetic backgrounds, whereas 4AL QTL (TaMKK3-A) interacted with environments only. The two QTLs showed additive effects on PHS resistance, indicating pyramiding these two QTLs can increase PHS resistance. To improve breeding selection efficiency, genomic prediction using genome-wide markers and marker-based prediction (MBP) using selected trait-linked markers were conducted in the association panel. Among the four genomic prediction methods evaluated, the ridge regression best linear unbiased prediction (rrBLUP) provides the best prediction among the tested methods (rrBLUP, BayesB, BayesC and BayesC0). However, MBP using 11 significant SNPs identified in the association study provides a better prediction than genomic prediction. Therefore, for traits that are controlled by a few major QTLs, MBP may be more effective than genomic selection.

The fungus Fusarium graminearum (Schwabe) causes Gibberella ear rot in maize, resulting in accumulation of harmful mycotoxins in the grain. Disease severity and pericarp/aleurone dehydrodiferulic acid content are negatively correlated. Furthermore, quantitative trait locus mapping (QTL) identified colocalization between QTL for both traits. A candidate gene approach was employed to identify the genes responsible for the observed colocalization. Candidate genes selected on the basis of their putative involvement in various aspects of cell wall DFA accumulation were mapped in silico using the maize genome sequence. Polymorphisms were discovered in putative genes and converted to molecular markers. The in silico mapping effort was successful in predicting map locations of the analyzed sequences, and the segregation of certain marker alleles could explain variation for Gibberella ear rot severity and pericarp-aleurone DFA content.

Doctor of Philosophy / Department of Agronomy / Guihua Bai / Growing resistant cultivars is an economically effective method to control wheat disease Fusarium head blight (FHB) caused by Fusarium graminearum. Ninety-five wheat lines mainly from China and Japan were evaluated for resistance to initial infection (type I), spread of symptoms within a spike (type II), and deoxynivalenol (DON) accumulation in infected grains (type III). Most of lines were resistant or moderately resistant, 15 lines had DON content lower than 2 ppm and six lines showed a high level of resistance for all the three types. Deoxynivalenol content was significantly correlated with type II, but not type I resistance. Fifty-nine of the ninety-five lines were evaluated for genetic diversity on the basis of amplified fragment length polymorphism (AFLP) and simple sequence repeats (SSRs). Genetic relationships among these lines were consistent with pedigrees and their geographic distribution. Chinese lines had broader genetic diversity than Japanese lines. Sumai 3 is a widely used Chinese variety for FHB-resistant breeding in the US and elsewhere. Haplotype patterns of the SSR markers linked to FHB resistance quantitative trait loci (QTL) on chromosomes 3BS, 5AS and 6BS of Sumai 3 indicated that only a few Sumai 3 derivatives carry all of these Sumai 3 QTL. SSR data also suggested that these QTL in Sumai 3 were derived from Chinese landrace Taiwan Xiaomai. Some highly resistant lines may carry novel QTL for FHB-resistance QTL, and need further investigation. A mapping population of 139 recombinant inbred lines derived from the cross of Wangshuibai (resistant Chinese landrace)/Wheaton (susceptible cultivar) was genotyped with more than 1300 SSR and AFLP markers. Five QTL for type I resistance were detected on chromosome arms 3BS, 4BS, 5DL, 3AS, and 5AS; seven QTL for type II resistance on 3BS, 1AL, 5AS, 5DL, 7AL, and 3DL; and seven QTL for type III resistance on 3BS, 5AS, 1AS, 5DL, 1BL, and 7AL. These QTL together explained 31.7%, 64%, and 52.8% of the phenotypic variation for FHB type I, II, and III resistance, respectively. QTL on 5AS, the distal end of 3BS, and 5DL contributed to all three types of resistance. FHB resistance QTL identified in Wangshuibai can be used in developing wheat cultivars with enhanced FHB resistance by pyramiding FHB resistance QTL from other sources.

Doctor of Philosophy / Department of Plant Pathology / James C. Nelson / The aim of quantitative trait locus (QTL) mapping is to identify association between DNA marker genotype and trait phenotype in experimental populations. Many QTL mapping methods have been developed to improve QTL detecting power and estimation of QTL location and effect. Recently, shrinkage Bayesian and penalized maximum-likelihood estimation approaches have been shown to give increased power and resolution for estimating QTL main or epistatic effect. Here I describe a new method, shrinkage interval mapping, that combines the advantages of these two methods while avoiding the computing load associated with them. Studies based on simulated and real data show that shrinkage interval mapping provides higher resolution for differentiating closely linked QTLs and higher power for identifying QTLs of small effect than conventional interval-mapping methods, with no greater computing time. A second new method developed in the course of this research toward increasing QTL mapping efficiency is the extension of multi-trait QTL mapping to accommodate incomplete phenotypic data. I describe an EM-based algorithm for exploiting all the phenotypic and genotypic information contained in the data. This method supports conventional hypothesis tests for QTL main effect, pleiotropy, and QTL-by-environment interaction. Simulations confirm improved QTL detection power and precision of QTL location and effect estimation in comparison with casewise deletion or imputation methods.

京都大学 / 0048 / 新制・論文博士 / 博士(農学) / 乙第13343号 / 論農博第2886号 / 新制||農||1079(附属図書館) / 学位論文||R2||N5250(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 奥本 裕, 教授 白岩 立彦, 教授 森 直樹 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第21377号 / 農博第2301号 / 新制||農||1069(附属図書館) / 学位論文||H30||N5150(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 奥本 裕, 教授 白岩 立彦, 教授 稲村 達也 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

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