Bioinformatics approaches to analysing RNA mediated regulation of gene expression [Elektronische Ressource] / Liam Childs

Liam Childs

Sujets

• Biologie

Informations

• Publié par: universitat_potsdam
• Publié le: 01 janvier 2009
• Nombre de lectures: 29
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Bioinformatics approaches to
analysing RNA mediated
regulation of gene expression
Dissertation

zur Erlangung des akademischen Grades
"doctor rerum naturalium" (Dr. rer. nat.)

eingereicht im
Institut für Biochemie und Biologie an der
Mathematisch-Naturwissenschaftlichen Fakultät der
Universität Potsdam



LIAM CHILDS

Arbeitsgruppe Bioinformatik
Max-Plank-Institut für Molekulare Pflanzenphysiologie

Potsdam, den 13.07.2009

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Published online at the
Institutional Repository of the University of Potsdam:
URL http://opus.kobv.de/ubp/volltexte/2010/4128/
URN urn:nbn:de:kobv:517-opus-41284
http://nbn-resolving.org/urn:nbn:de:kobv:517-opus-41284
Acknowledgements
Dirk Walther is certainly one of the best supervisors I’ve ever had. He gave me the freedom
to pursue my own ideas and goals whilst providing all the necessary help and support when
needed. I have a sneaking suspicion that, if I didn’t play the drums, I may not have been
chosen to fill this PhD position. Nevertheless, studying under Dirk and playing in a kick-arse
rock/pop/punk/funk/blues/jazz band together has made the past three years, although so very
far from home, a very happy and fulfilling experience. To work at such an institute, in the
company of great scientific minds, has helped my scientific thinking through a colossal
improvement. I still have far to go, but I start my post-doctoral efforts from a very solid basis.
I would also like to thank my official university supervisor Joachim Selbig. Thanks to the
whole of AG Bioinformatics; Christian Schudoma, Zoran Nikoloski and Patrick May for all
the help provided, and also to Manuela Hische, Sergio Grimbs, Sebastian Klie, Georg Basler,
Jan-Ole Christian, Tanja Gärtner, Henning Redestig, Pawel Durek, Jan Hummel and
Xiaoliang Sun for the good times and great company.
Thanks also to Thomas Altmann and Hanna Witucka-Wall for their help and for my
involvement in their project along with Karl Schmid and Torsten Günther.
Quick thanks to Marco Ende and Peter Krüger for technical support.
Thanks to two very special friends Jan Lisec and Sandra Witt for the company, both
wonderfully immature and entertaining, at lunchtime and during the jamming sessions.
I thank my family for their support; Mum, Dad and Owen, and Sean for shedding a little
brilliance on my projects whenever I was stuck. 16,110 km is no small distance and I miss
you all very much. And finally, to my girlfriend Julia, my thanks to you can not be written
down on paper ;).

iii
Selbständigkeitserklärung


Hiermit erkläre ich, dass ich die vorliegende Arbeit selbständig und unter
Verwendung keiner anderen als den von mir angegebenen Quellen und
Hilfsmitteln verfasst habe.

Ferner erkläre ich, dass ich bisher weder an der Universität Potsdam noch
anderweitig versucht habe, eine Dissertation einzureichen oder mich einer
Doktorprüfung zu unterziehen.









Potsdam, 13 July 2009



____________________________________

Liam Childs
v
Contents
Abstract ................................................................................................................................................... xi
Lay Abstract .................................................. xii
Zusammenfassung .............................................................................................................................................. xiv
Chapter 1. Introduction ........................................................................ 1
1.1. What is RNA? .............................................................................................................................................. 2
1.1. The Central Dogma .... 2
1.2. The RNA world hypothesis .......................................................................................................................... 3
1.3. Discovery of new ncRNA ............................ 4
1.3.1. miRNA .................................................................................................................................................. 5
1.3.2. snoRNA ................ 6
1.3.3. Riboswitches......................................................................................................................................... 7
1.3.4. Ribozymes ............ 8
1.3.5. Artificial ncRNA ................................................................................................................................... 9
1.4. Arabidopsis ................................................................................................................................................. 9
1.4.1. ncRNA in Arabidopsis .......................... 9
1.5. Key concepts ............................................................................................................................................. 11
1.5.1. Folding RNA ...... 11
1.5.2. Graphs and graph theory ................................................................................................................... 14
1.5.3. State machines.................................................................................................................................... 15
1.5.4. Hidden Markov Models ...................................................................................................................... 15
1.5.5. Covariance models ............................. 16
1.5.6. Microarrays ....................................................................................................................................... 17
1.5.7. Support vector machines .................... 17
1.5.8. Association studies ............................................................................................................................. 18
1.6. Outline ...................................................... 19
Chapter 2. Arabidopsis genotyping .................................................................................................................... 21
2.1. Abstract ..................................................................................................................... 21
vii
2.2. Introduction .............................................................................................................................................. 22
2.3. Methods ..................... 25
2.3.1. Selection of accessions ....................................................................................................................... 25
2.3.2. Plant material preparation for phenotypic analysis .......... 25
2.3.3. Plant material preparation for genotypic analysis ............................................................................ 27
2.3.4. SFP identification .............................................................................................................................. 28
2.3.5. Analysis of functional gene categories ............................... 30
2.3.6. Detection of duplications and deletions ............................................................................................. 30
2.3.7. Whole genome haplotyping ................................................ 31
2.3.8. Identification of selective sweeps ....................................................................... 31
2.3.9. SFP-trait associations ........................................................................................................................ 32
2.4. Results ....................................................... 33
2.4.1. Patterns of SFP diversity ................................................................................................................... 33
2.4.2. Deletions and duplications ................. 37
2.4.3. Population structure analysis ............................................................................................................ 38
2.4.4. Choice of phenotypic traits ................ 38
2.4.5. Analysis of selective sweeps ............................................................................................................... 39
2.4.6. Association mapping .......................... 41
2.5. Discussion ................................................................................................................................................. 42
2.5.1. Genomic data ..... 42
2.5.2. Associations ....................................................................................................................................... 46
2.5.3. Natural selection mapping versus molecular genetics. ...... 48
Chapter 3. ncRNA functional prediction ........................................................................