Del modelo de Harrod-Domar al modelo neoclásico de crecimiento

Future research in PRKG2 will focus on intermediates in the PRKG2, SOX9 signaling system. In Angus dwarves, work is on going in collaboration with the University of Nebraska to understand how the R678Z PRKG2 mutation alters protein localization in growth plate and other tissues. Continued analysis of expression data is needed to understand how PRKG2 mediated signaling may play a role in MAPK, WNT, or calcium cascades. If confirmed, functional studies would be needed to demonstrate how PRKG2 is altering biological processes in the growth plate. Besides continued research in bone, studies of PRKG2 function in skeletal muscle and lung are particularly interesting areas for further investigation. Since PRKG2 regulates proliferation, it may alter the rate of myogenesis. In the lung, PRKG2 acts as an important regulator of the cystic fibrosis transmembrane receptor system. Therefore, PRKG2 has important implications to cystic fibrosis research. The global expression of PRKG2 would suggest the potential for conserved biological processes with different contexts on a tissue-to-tissue basis. A comparison of gene expression across tissues could yield key pathway components of the PRKG2 signaling system that are used across tissues.

CONCLUSIONS

In conclusion, a causative mutation for Angus dwarfism was discovered in the kinase domain of PRKG2. Linkage mapping, real-time PCR expression data,

breeding experiment results, and microarray results all strongly support this conclusion. The genetic test developed to assay the R678Z PRKG2 mutation was 100% accurate in predicting the dwarfism status of six calves produced in the breeding experiment. The microarray data also independently confirmed the real- time PCR results for COL2 and COL10 over-expression in dwarves. The immediate implication of these results is the development of a genetic marker to determine dwarf carriers prior to the production of dwarf calves. The test will save producers considerable profit for each dwarf carrier identified. Long-term implications of PRKG2 data may provide insight into the process of growth plate development.

ACKNOWLEDGEMENTS

My time at Iowa State University has been a time of great growth in my life as a scientist, but more importantly, as a person. I think this aspect gets lost in graduate student training, but it is a part of my training I am very grateful for. To everyone who has helped me, thank you. I cannot recall everyone who has influenced me at ISU, but I will do my best to give credit where it is due. I apologize to those who I have forgotten as so many have been part of my learning experience.

To my major professor, Jim Reecy, thanks for your guidance and support. Thank you for answering my questions at all hours of the day and always keeping your door open. We have been through a lot together. It is my sincerest hope that I will learn to grow as a professor as I have seen you grow during my time as a student. I hope I can mentor students and juggle research and life as well as you have. I thank you for your time, patience, and more than anything, I thank you for all of the extra things that you have done to make your lab more like a family than a job. What I have gained here has changed my life and I am not only a better scientist but a better man for it. I look forward to many years of scientific discussion and friendship.

To my Ph.D. program of study committee members: Lloyd Anderson, Jack Dekkers, Ken Koehler, Carolyn Komar, and Max Rothschild, thank you for your help and guidance. I would like to thank Jack for his guidance and support, especially at the beginning of my program. You treated me like one of your own students, and I always appreciated that. Max, I am grateful for your help and guidance. You also took me on as if I was one of your students. Your advice is always greatly valued by

me. The leadership skills that I learned working with you as an advisor for the ISU Bass Anglers will shape me for years to come. Hopefully, I will make enough money someday to afford a fishing trip to Canada! Last, I want to thank Lloyd Anderson for jumping onto my committee at the very end to fill in.

Many collaborators have assisted me in research. A few need to be singled out here. Dr. Mike Gonda, Wisconsin/ North Carolina State, supplied me with several publications and protocols throughout my Ph.D. Mike, thanks for your help. Drs. Michel Georges, Wouter Coppieters, Bernard Grisart, and Carole Charlier took me as one of their own at the University of Liege during my stay in 2004. I thank them for their warmth and support. Last, I need to thank Drs. George Shook and Brian Kirkpatrick at the University of Wisconsin for getting me started in genetics. I especially need to thank George for his guidance and support as a mentor. George, you helped me to find a passion in my life and gave me opportunities that opened many doors. Thank you for helping me find my way.

Reecy lab, thank you for your friendship and support. Jackie Potts, David Morris, Bishnu Mishra, Artur Rosa, Sam Anderson, Cari Steelman, Christian Paxton, Karen Langner, Jose Rodriguez, Ying-Zhi Xu, Dinesh Kumar, Ranjit Kataria, LaRon Hughes, Eric Fritz, Satyanarayana Rachagani, Ye Cheng, Matt Schneider, Julie Collins, Brandon Cornelius, Andrea Moe, Nicole Rutscher, Jessica Frerichs, Aracely Acevado, Susan Piripi, Abebe Hasan, Mary Sue Mayes, and Rachel Sippy- to each of you, I am grateful. Abebe and JR, thanks for always making time to help me with SAS and statistics. Sam, you were my mentor as a student, thank you for that. To those of you I taught in the lab, you gave me the greatest gift-to be a teacher. I am

indebted for what you taught me and for your patience. It was never a dull moment! JR, Ranjit and Dinesh, thanks so much for covering for me when I needed help after my mom’s accident. Mary Sue, thank you for your understanding, support and kindness. Many of you set aside time to help me with research and I want you to know it was appreciated.

To the graduate students at Iowa State, many thanks. Discussion with other students is where most of the real science learning took place. I need to point out a few students who spent many hours with me. Joe McElroy, thank you for the many discussions. I must have driven Joe nuts, but our discussions were always thought provoking. Benny Mote, thank you for all of the help in the lab. I think our meeting of the minds, AKA, “cuss and discuss” sessions taught me more about hands on molecular techniques than any book ever has or will. I also need to thank Jing Wang, Hauke Thomsen, Jong-Joo Kim, Ali Toosi and Radu Totir for all of their assistance. When ever I had statistical or computational problems, these students and post-docs spent as much time as I needed to help out. It was kind efforts like this that truly built a great learning environment in graduate school for me.

To the animal science/ genetics faculty, I need to make several acknowledgements. First, I need to thank Rohan Fernando for always taking time to help me. Rohan, I always have a lot of questions about how various methods work. I hope you know how fascinated I was to learn as much detail as possible about our linkage mapping work. It was fun to learn with you one-on-one. Linda Wild, thank you for all of your help and support. I enjoyed our many discussions. A long overdue thank you goes out to Rod Berryman, Marshall Ruble and the ISU farm

staff. Without you guys, I never would have been able to do the really important work, showing how the genetics works in live animals. Rod, thank you for your help with the dwarf cattle and all the random stuff in between. Marshall, thank you for your patience and assistance moving and managing the dwarf calves, recipient cows, etc. I often had last minute obligations arise when I was working with the calves, and I appreciated your flexibility.

Most of all, I need to thank my friends and family. To my best and most faithful friends who slugged it out with me and kept life interesting, I am always at your service. We all went through a lot, but we did it together. Jason, Marie, Jamie, Oliver, Colin, Ruth, Liz and Benny, thank you for everything. Do not forget me when you are successful and famous someday. I need to thank the Frerichs for their support and taking me in as if I was one of their own. Benny, thanks for the assistance, support, and help through everything. Thank you for always making time to discuss research and life. I will not forget going to the farm at 5AM to scan hogs for Jack and then going to quantitative genetics after staying up to 3AM to finish the homework. It took a little Mountain Dew to get through these times! There were days when I think we were both ready to say the heck with this, but we kept each other going. It’s a good thing there was one other farm kid around to talk to! To my family, words can not describe how much I love you and what your support has meant to me. Mom and dad, sorry I had to go to Iowa. I know it wasn’t easy at first, but it was good for me and I am better for it. Thank you for the love and support. Last, I need to thank my brother Mike for the hours of discussion about everything. Thank your for your support, friendship and love. You have been a role

model to me at many times. What I have done within this thesis, I dedicate to you and all of my family. Do not leave anything undone because it is hard. If you love it and it is worth doing, follow your dreams always.