Computational Identification of Recessive Mutations in Cancers using High Throughput SNP-arrays

This thesis presents a highly sensitive genome wide search method for recessive mutations. The method is suitable for distantly related samples that are divided into phenotype positives and negatives. High throughput genotype arrays are used to identify and compare homozygous regions between the cohorts. The method is demonstrated by comparing colorectal cancer patients against unaffected references. The objective is to find homozygous regions and alleles that are more common in cancer patients. We have designed and implemented software tools to automate the data analysis from genotypes to lists of candidate genes and to their properties. The programs have been designed in respect to a pipeline architecture that allows their integration to other programs such as biological databases and copy number analysis tools. The integration of the tools is crucial as the genome wide analysis of the cohort differences produces many candidate regions not related to the studied phenotype. CohortComparator is a genotype comparison tool that detects homozygous regions and compares their loci and allele constitutions between two sets of samples. The data is visualised in chromosome specific graphs illustrating the homozygous regions and alleles of each sample. The genomic regions that may harbour recessive mutations are emphasised with different colours and a scoring scheme is given for these regions. The detection of homozygous regions, cohort comparisons and result annotations are all subjected to presumptions many of which have been parameterized in our programs. The effect of these parameters and the suitable scope of the methods have been evaluated. Samples with different resolutions can be balanced with the genotype estimates of their haplotypes and they can be used within the same study.

Venäjän politiikka ja perustuslaki : Tutkimus Venäjän perustuslakikäsitteistön kehityksestä 1900-luvulla

Constitutional politics in Russia, a conceptual history study of the constitutional rhetoric in the 20th century In April 2006 the Russian Constitution had its 100th anniversary. Following its late start, five constitutions have been adopted. The great number of constitutions is partly explained in my work by the fact that Russia s political system has changed many times, from one state system to another. From a monarchical state power, it changed first, with the October revolution, into the Russian Socialist Federal Soviet Republic, and after that, in 1924, into the Union of Soviet Socialist Republics. In 1991, the Russian Federation was established. The great number of constitutions can also be explained by the fact that in a one-party system, constitutional concepts became one of the most important instruments for introducing political programmes. When the political unity of the state was not only restricted by the Constitution, but also by the party ideology, the political debates concerning constitutional concepts were the key discussions for all the reformative pursuits of Soviet politics. It can be said that, in the Soviet Union, almost all political discourses dealt with constitutional concepts. In the context of restricted unity, the constitutional concepts were the most important tools to argue and create a basis for a new presentation and new political programmes. Thus, the basic feature of the Soviet political discourses has been a continuous competition regarding the constitutional concepts. By defining the constitutional concepts, a new, the political elites wanted especially to redefine, their own way, the traditional meanings of the October 1917 Revolution, and to differentiate them from those of the preceding period of power. From a methodological point of view, I argue that the Russian constitutional concepts make a conceptual historical approach very suitable, and change the focus on history. This approach studies history in contemporary contexts which follow after each other, and whose texts are the main research target. The picture of history is created through the interpretation of the original sources of contemporary contexts. Focusing on the dynamic and traditional characteristic of Russian constitutional concepts, I refer to a certain kind of value and the task of these concepts to justify and define the political and societal unity in every situation. This is done by combining the pursued future orientation of constitutional unity with the new acts of preservation of the traditional principles of the revolution. The different time layers of the constitutional concepts, the past, the present and the future, are the key aspects of storytelling in justifying the continuity and redefining the constitutional unity for the sake of reform. These aspects of constitutional concepts, in addition to all the other functions, have been the main elements of the argumentative structure of acting against opponents.