This work was carried out at the Department of Medical Genetics, Haartman Institute, University of Helsinki during 1997-2000. I wish to express my warmest gratitude to all those who made it possible:
Lauri Aaltonen, my supervisor, for introducing me to the field of medical genetics. I am very grateful that I had the opportunity to join his research group and learn so much during this period. Besides the scientific discussions, I will always remember those intense debates concerning ice-hockey.
Albert de la Chapelle, my second supervisor, for his enthusiasm for the research, his guidance and encouraging attitude towards this work.
Juha Kere, Leena Peltonen and Pertti Aula, the former and present heads of the Department of Medical Genetics for providing me with excellent working facilities.
Anu Jalanko and Hannu Sariola, the official pre-examiners of this study for their valuable comments.
Anu Loukola and Virpi Launonen for their encouragement and friendship, and for helping me through all those days, when smad went mad and everything was unlinked. We really had many (extremely!) enjoyable moments at work as well as outside our working hours!
Egle Avizienyte, Akseli Hemminki and Reijo Salovaara for their friendship during these years. I am especially grateful to them for their warm welcome when I first came to the "Peutz-Jeghers team".
Heikki Järvinen, Jukka-Pekka Mecklin, Pertti Sistonen, Ilmo Kellokumpu, Päivi Peltomäki, and Paula Kristo, whose help and experience were of great value during this study.
Marie Johansson, Päivi Laiho, Kirsi Laukkanen and Annika Lahti for their skillful technical assistance in the lab as well as many cheerful lunch breaks in the UniCafe.
Sinikka Lindh and Siv Lindroos for their sincere friendship, and for helping me patiently no matter how busy they were.
Elina Kirjavainen and Minna Maunula for their help in many practical matters. Elvi Karila, Anita Hottinen and Susanna Anjala for sequencing service. Kaija Collin, Liisa Suksi and Taija Poikonen for cell culturing and DNA extraction. Tuula Lehtinen for helping me with the JP patient data.
Charis Eng, James Howe, Christopher I. Amos, Ian Tomlinson and Debbie Marsh for excellent collaboration.
The co-authors in different studies: Steven Bevan, Walter F. Bodmer, Stacey Caron, Karen A. Cleary, Sally E. Cottrell, Patricia L.M. Dahia, Malcom G. Dunlop, Diana Eccles, Shirley V. Hodgson, Richard S. Houlston, Kathryn L. Lunetta, Patrick Lynch, David Markie, Frank A. Mitros, Kay Neale, Robin Phillips, John C. Ringold, Paul Rozen, Edwin M. Stone, Robert W. Summers, Sapna Syngal, Nathalie J. van Orsouw, Jan Vijg, and Zimu Zheng.
My previous colleagues and my present friends; Minna Veini, Sari Rantanen and Terhi Kiviranta for sharing many hobbies and unforgettable moments with me.
All my colleagues at the Department of Medical Genetics for creating such a nice atmosphere.
Donald Smart for the language revision of this thesis.
My parents Aila-Riitta and Rolf for their love and support; and my brother Kristian and my sister Emma for their friendly criticism and many enjoyable moments together.
My godfather Arvo for his encouragement and great interest in my career.
Mikko Tammiruusu for his love, support, and understanding during these years. I really didn't make it easy...
Aki Ylä-Soininmäki for his care, optimism and generous help during the last few months.
This work was financially supported by the Finnish Cancer Society, the Ida Montin Foundation, the Emil Aaltonen Foundation, the Finnish Cultural Foundation, the Academy of Finland and the Research and Science Foundation of Farmos.