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Systems genetics studies for unraveling genetic basis of complex traits have been one of the most propitious research area with the advance of high-throughput biotechnologies. This thesis presents several computational and statistical challenges in effective design and analysis of systems genetics studies and present novel methodological advances and corresponding results in several specific contexts of systems genetics studies. First, I present an extensive haplotype analysis on a recently collected catalogue of genetic variation among inbred mouse strains, which revealed the contribution from ancestral subspecies, haplotype block structure, and complex history of each genomic segments among the inbred mouse strains. In addition, I accurately imputed the uncollected genotypes in the resource by developing a novel and efficient genotype imputation method which adaptively learns parameters from data using an Expectaion-Maximuzation (EM) algorithm. Our method is demonstrated to outperform previous methods in both mouse and human data. Statistical analyses in systems genetics studies are often confounded by unmodeled factors such as heterogeneous sample structure. Recent studies suggested that mixed models correct for the sample structure in association mapping, but the available methods suffer from substantial computational cost to be applied in genome- wide association mapping. I developed the Efficient Mixed Model Association (EMMA), which takes advantage of the invariant structure of eigenvectors in applying mixed models for association mapping, which substantially increase the computational efficiency in several orders of magnitude. Our method was shown to successfully reduce inflated false positives in in silico genome-wide association mapping of inbred mouse strains involving hundreds of thousands of markers. I further extend EMMA to accommodate even larger scale of genome-wide association mapping in humans, typically involving several thousands or more individuals, and demonstrate that the method consistently eliminates the significant over-dispersion of test statistics across multiple human data sets. The method has been further employed in correcting for a different type of confounding effects in expression studies. I developed a novel mixed-model method that corrects for the spurious associations and trans- regulatory bands caused by systematic confounding effects using inter-sample correlation of expression measurements. Finally, in the design of association studies using inbred strains, I propose a novel trait mapping strategy using hybrid mouse diversity panel (HMDP). By integrating classical inbreds and multiple sets of recombinant inbreds while precisely accounting for the sample structure using high-density markers with EMMA, the proposed design is shown to much more powerfully and precisely identify previously known associations than previous approaches.

As a Vietnam veteran film director, Oliver Stone has made several controversial films on the Vietnam War and the 1950s. Among his filmography, we can categorize Platoon (1986), Born on the Fourth of July (1989), and Heaven and Earth (1993)-Stone's so called Vietnam Trilogy-as the most direct depictions of the war and its aftermath, whereas The Doors (1991), JFK (1991), and Nixon (1995) examine the broader political and cultural dimension of the war and the era. Throughout his Vietnam films, Stone struggles to find the new America's identity by studying the historical meaning of its past events and characters, because he knows that the correct interpretation of the past based upon a balanced political perspective is a beginning of understanding who Americans are, and predicting what the country will be in the new millennium. Stone shows the progression of his political awareness from American Self to Vietnamese Other in his Vietnam Trilogy. In Platoon, by employing the bildungsroman form and a Christian theme, Stone examines a naive young soldier's initiation into the war. However, given an absence of historical perspective based upon the political awareness on the war, the film's narrative style and thematic structure do not work satisfactorily. In fact, Platoon replaces historical understanding of the war with a psychological interpretation-the struggle between good and evil. In Bom on the Fourth of July, Stone examines a paralyzed Vietnam veteran's political initiation to American culture and people. At first, the protagonist Ron Kovic is a victim of both his family and his country; later he rebuilds the value of American community based upon the power of political awareness and the understanding on the war and others. At the end of the film, he is projected as the savior of the nation. In Heaven and Earth, though Stone for the first time tries to dramatize the story from the viewpoint of the political other--a female Vietnamese, the film’s focus is still primarily on America. With the heroine Le Ly who has been victimized not only by American soldiers but also by the Vietcong, the film deeply relies on the redemptive power of the heroine. Though the heroine finds her victory in her heart, the film also cannot touch the historical wholeness of the war and does not shed tears for the Vietnamese victims. Therefore, it seems that Stone focuses on the moral redemption of American in the hand of a former enemy. Although Oliver Stone has contributed to the understanding of the war and its effect, he still has not depicted the balanced wholeness of the war based upon historical perspective. It seems that Stone cannot transcend the Americanized context of his political vision. Therefore, it can be said that Stone’s Vietnam films are still work-in-progress versions in American film and an understanding of the Vietnam War based upon a balanced historical perspective can only be achieved by the Vietnamese themselves.