@article{Helmreich2010,
  author    = {Helmreich, Ernst J. M.},
  title     = {Ways and means of coping with uncertainties of the relationship of the genetic blue print to protein structure and function in the cell},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68006},
  year      = {2010},
  abstract  = {As one of the disciplines of systems biology, proteomics is central to enabling the elucidation of protein function within the cell; furthermore, the question of how to deduce protein structure and function from the genetic readout has gained new significance. This problem is of particular relevance for proteins engaged in cell signalling. In dealing with this question, I shall critically comment on the reliability and predictability of transmission and translation of the genetic blue print into the phenotype, the protein. Based on this information, I will then evaluate the intentions and goals of today's proteomics and gene-networking and appraise their chances of success. Some of the themes commented on in this publication are explored in greater detail with particular emphasis on the historical roots of concepts and techniques in my forthcoming book, published in German: Von Molek{\"u}len zu Zellen. 100 Jahre experimentelle Biologie. Betrachtungen eines Biochemikers},
  subject      = {Genetik},
  language  = {en}
}
@phdthesis{Emmert2010,
  author    = {Emmert, Wulf-Kristian},
  title     = {Rachitis-{\"a}hnliche Symptome bei nigerianischen Kindern aus der Ethnie der Gbagyi in der s{\"u}dwestlichen Region Kadunas: Identifizierung des biochemischen Defekts, Sammeln von epidemiologischen Daten und Beschreibung des klinischen Bildes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-48354},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Zielsetzung: In einer Population im Westen der nigerianischen Stadt Kaduna wurden seit 20-30 Jahren vermehrt Kinder mit einer deformierenden Knochenerkrankung registriert. Ziel der Studie war, eine Diagnose zu stellen und Risikofaktoren f{\"u}r die Erkrankung zu identifizieren. Studiendesign: 26 Familien aus 20 D{\"o}rfern wurden in die Studie einbezogen. In einer nicht-randomisierten Fall-Kontroll-Studie wurden 53 erkrankte Kinder mit 48 gesunden sowie 16 fraglich erkrankten Geschwistern anhand ihrer Ergebnisse aus Anamnese, klinischer Untersuchung und Laborchemie miteinander verglichen. Ebenfalls wurden Daten von 24 V{\"a}tern und 36 M{\"u}ttern ausgewertet. Weitere Untersuchungen umfassten Ern{\"a}hrung, Anthropometrie, Umweltfaktoren und Genetik der teilnehmenden Familien. Ergebnisse: Die betroffenen Kinder wiesen deutliche Rachitissymptome auf, bei allen lag eine Kalzium-defiziente Rachitis vor. Zwischen den Laborergebnissen von Fall- und Kontrollgruppe bestanden signifikante Unterschiede, nicht jedoch zwischen der Gruppe der fraglichen F{\"a}lle und der Kontrollgruppe. In der Fallgruppe waren die Serumspiegel von Kalzium und 25-Vit. D signifikant niedriger, die Serumspiegel von 1,25-Vit. D, ALP und PTH signifikant h{\"o}her als in der Kontrollgruppe. Bei den Eltern zeigten die M{\"u}tter insbesondere in der Stillzeit signifikant niedrigere Kalzium- und signifikant h{\"o}here 1,25- Vit. D- und PTH-Serumspiegel als die V{\"a}ter. Als Ursache f{\"u}r den Kalziummangel der Studienteilnehmer konnte eine kalziumarme und phytatreiche Di{\"a}t der Familien identifiziert werden. Hinweise auf einen gesunkenen Lebensstandard und eine Abnahme der Bodenqualit{\"a}t erkl{\"a}ren die in den letzten Jahrzehnten stark gestiegene Pr{\"a}valenz der Erkrankung. Bei weitgehend gleichen Ern{\"a}hrungs- und Umweltfaktoren innerhalb einer Familie konnten keine individuellen Faktoren identifiziert werden, die bei einzelnen Familienmitgliedern zum Ausbruch der Erkrankung f{\"u}hrten. Trotz einzelner Hinweise auf eine m{\"o}gliche genetische Pr{\"a}disposition war kein einheitliches Vererbungsmuster in den Stammb{\"a}umen der Familien erkennbar. Schlussfolgerung: Neben dem Hauptfaktor einer kalziumarmen Ern{\"a}hrung m{\"u}ssen weitere Faktoren f{\"u}r eine Kalzium-defiziente Rachitis vorliegen. Mehrere Hinweise deuten auf eine multifaktorielle Genese der Erkrankung hin. Die noch offenstehenden Fragen sollten durch weitere Studien gekl{\"a}rt werden, um die richtigen Maßnahmen f{\"u}r Pr{\"a}vention und Therapie zu treffen.},
  subject      = {Rachitis},
  language  = {de}
}
@phdthesis{Vershenya2010,
  author    = {Vershenya, Stanislav},
  title     = {Quantitative and qualitative analyses of in-paralogs},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-51358},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {In our analysis I was interested in the gene duplications, with focus on in-paralogs. In-paralogs are gene duplicates which arose after species split. Here I analysed the in-paralogs quantitatively, as well as qualitatively. For quantitative analysis genomes of 21 species were taken. Most of them have vastly different lifestyles with maximum evolutionary distance between them 1100 million years. Species included mammals, fish, insects and worm, plus some other chordates. All the species were pairwised analysed by the Inparanoid software, and in-paralogs matrix were built representing number of in-paralogs in all vs. all manner. Based on the in-paralogs matrix I tried to reconstruct the evolutionary tree using in-paralog numbers as evolutionary distance. If all 21 species were used the resulting tree was very far from real one: a lot of species were misplaced. However if the number was reduced to 12, all of the species were placed correctly with only difference being wrong insect and fish clusters switched. Then to in-paralogs matrix the neighbour-net algorithm was applied. The resulting "net" tree showed the species with fast or slow duplications rates compared to the others. We could identify species with very high or very low duplications frequencies and it correlates with known occurrences of the whole genome duplications. As the next step I built the graphs for every single species showing the correlation between their in-paralogs number and evolutionary distance. As we have 21 species, graph for every species is built using 20 points. Coordinates of the points are set using the evolutionary distance to that particular species and in-paralogs number. In mammals with increasing the distance from speciation the in-paralogs number also increased, however not in linear fashion. In fish and insects the graph close to zero is just the same in mammals' case. However, after reaching the evolutionary distances more than 800 million years the number of inparalogs is beginning to decrease. We also made a simulation of gene duplications for all 21 species and all the splits according to the fossil and molecular clock data from literature. In our simulation duplication frequency was minimal closer to the past and maximum in the near-present time. Resulting curves had the same shape the experimental data ones. In case of fish and insect for simulation the duplication rate coefficient even had to be set negative in order to repeat experimental curve shape. To the duplication rate coefficient in our simulation contribute 2 criteria: gene duplications and gene losses. As gene duplication is stochastical process it should always be a constant. So the changing in the coefficient should be solely explained by the increasing gene loss of old genes. The processes are explained by the evolution model with high gene duplication and loss ratio. The drop in number of in-paralogs is probably due to the BLAST algorithm. It is observed in comparing highly divergent species and BLAST cannot find the orthologs so precisely anymore. In the second part of my work I concentrated more on the specific function of inparalogs. Because such analysis is time-consuming it could be done on the limited number species. Here I used three insects: Drosophila melanogaster (fruit y), Anopheles gambiae (mosquito) and Apis mellifera (honeybee). After Inparnoid analyses and I listed the cluster of orthologs. Functional analyses of all listed genes were done using GO annotations and also KEGG PATHWAY database. We found, that the gene duplication pattern is unique for each species and that this uniqueness is rejected through the differences in functional classes of duplicated genes. The preferences for some classes reject the evolutionary trends of the last 350 million years and allow assumptions on the role of those genes duplications in the lifestyle of species. Furthermore, the observed gene duplications allowed me to find connections between genomic changes and their phenotypic manifestations. For example I found duplications within carbohydrate metabolism rejecting feed pattern adaptation, within photo- and olfactory-receptors indicating sensing adaptation and within troponin indicating adaptations in the development. Despite these species specific differences, found high correlations between the independently duplicated genes between the species. This might hint for a "pool" of genes preferentially duplicated. Taken together, the observed duplication patterns reject the adaptational process and provide us another link to the field of genomic zoology.},
  subject      = {Duplikation},
  language  = {en}
}