|
|
Molecular Signature as Optima of Multi-Objective Function with Applications to Prediction in Oncogenomics
Aligerová, Zuzana ; Maděránková, Denisa (referee) ; Provazník, Ivo (advisor)
Náplní této práce je teoretický úvod a následné praktické zpracování tématu Molekulární signatura jako optimální multi-objektivní funkce s aplikací v predikci v onkogenomice. Úvodní kapitoly jsou zaměřeny na téma rakovina, zejména pak rakovina prsu a její podtyp triple negativní rakovinu prsu. Následuje literární přehled z oblasti optimalizačních metod, zejména se zaměřením na metaheuristické metody a problematiku strojového učení. Část se odkazuje na onkogenomiku a principy microarray a také na statistiku a s důrazem na výpočet p-hodnoty a bimodálního indexu. Praktická část je pak zaměřena na konkrétní průběh výzkumu a nalezené závěry, vedoucí k dalším krokům výzkumu. Implementace vybraných metod byla provedena v programech Matlab a R, s využitím dalších programovacích jazyků a to konkrétně programů Java a Python.
|
|
|
Studium pozičních kandidátních genů SERPINE1, LDHA a UBL5 ve vztahu k masné užitkovosti prasat
Weisz, Filip
This PhD thesis was focused on study SERPINE1, LDHA and UBL5 as positional candidate genes for meat performance traits in pigs. We detected SNP FN396538:g.566G>A in intron 3 and SNP NM_213910:c.612A>G in exon 3 (Ile159Val) in the SERPINE1 gene, which has been mapped at position 8.4 cM on the linkage map of chromosome 3. Association analyses were conducted on 12th -15th generation of Meishan x Large White (MLW) cross (n = 565) and on European wild boar x Meishan (W x M) F2 population (n = 333). Analyses performed across the entire MLW or in male animals did not show any trait significantly associated with the loci studied. In female animals, both SNPs were significantly associated with loin depth. In the entire W x M population and female animals, SERPINE1 was significantly associated with muscling, growth and fat accretion and in male animals with meat quality traits. In the studied populations, allele effects were in opposite directions, which imply that the SNPs are markers that are in linkage disequilibrium with causative mutations. To search for heterogenity of the LDHA gene we comparatively sequenced cDNA and the 5' flanking region where we detected 8 a 1 SNPs, respectively. We also found 2 different positions of poly(A) sequences in cDNA of LDHA by RACE. Association analyses performed for SNPs GL041338.1:c.49341G>C and FJ865398:c.795A>G did not show any significant association with the studied traits in the MLW population. The significant association of c.49341G>C with growth, fattening traits and muscling in Pietrain x Meishan (P x M) F2 population (n = 316) were found. Association analyses of c.795A>G revealed significant effect of this SNP on growth and fattening traits, fat accretion and muscling in W x M population. The UBL5 gene was studied by inverse PCR and totally 12 polymorphisms were observed. We detected 8 cDNA sequences of various lengths with different transcription start sites of the exon 1 and alternative splicing site between exon 1 and 2 and in 1 sequence also between exon 2 and 3. Alternative splicing between exon 2 and 3 causes shift of the ORF and occurrence of premature stop codon. Association analyses were performed for SNPs FR798948:g.2141C>T and FR798948:g.2778G>A on the MLW and the W x M populations. In the MLW population, SNP g.2141C>T was associated with average daily gain in test and SNP g.2778G>A with back fat thickness. In the W x M population, SNP g.2778G>A was associated with fat accretion, growth and fattening, muscling and SNP g.2141C>T with fat accretion. The SNPs within studied genes that were associated with performance traits are markers in linkage disequilibrium with causative mutation either in genes or in surrounding area.
|
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
|
| |
guest ::
