BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:The Long-legged mouse and the Impossible Hybrid – the genetics o
 f genome evolution in the mouse from stem cells to whole organisms  - Dr Y
 ingguang Frank Chan
DTSTART:20161003T150000Z
DTEND:20161003T160000Z
UID:TALK66609@talks.cam.ac.uk
CONTACT:46487
DESCRIPTION:The genome is in constant evolution. Despite this constant cha
 nge\, the genome also has to maintain essential functions. Discovering the
  evolutionary process underlying genome evolution is thus a central goal n
 ot only in evolutionary genetics\, but also in medicine. I will discuss tw
 o studies in the mouse\, where we take a systems genetics approach to unde
 rstand how the genome evolves in the mouse. First I will discuss the evolu
 tion of the “Longshanks mouse”\, a unique genetic resource created by 
 my collaborator Campbell Rolian at the University of Calgary. By subjectin
 g mouse to twenty generations of strong selection for increased tibia leng
 th\, he was able to generate mice with tibia as much as 25% longer than th
 eir unselected relatives. We have sequenced genomes of the selection pedig
 ree to allow us to not only identify the loci that changed under selection
 \, but also “replay the evolutionary tape” and uncover how the genome 
 reshapes itself locus by locus. I will also discuss our molecular genetics
  investigations into key developmental genes that contribute to such drast
 ic evolutionary response. In a second part I will discuss our novel approa
 ch of generating in vitro “crosses” using in interspecific F1 hybrid m
 ouse embryonic stem (ES) cells. Starting from an F1 hybrid ES cell line be
 tween Mus spretus and the laboratory mouse Mus musculus domesticus\, we ha
 ve developed a simple tissue culture system to generate mitotic recombinan
 ts with genome-wide random breakpoints. By bypassing hybrid sterility and 
 inviability\, we can now generate “Impossible Hybrid” mouse stem cells
  and directly investigate which genetic changes underlie species differenc
 es. We will present our proof-of-concept results\, where we show how to ef
 ficiently generate recombinant ES cell lines entirely in vitro without cro
 sses. By coupling in vitro crosses with FACS\, I will discuss our forward 
 genetic mapping experiments for stem cell traits that are now routine and 
 can be performed in as few as 6 days. This approach will make it possible 
 to create large genetic mapping panels of potentially any size from mouse\
 , or indeed human or other mammals with a robust tissue culture system. In
  doing so we identify an experimental way towards studying evolutionary sy
 stems biology in a mammalian system. Through these two examples I hope to 
 highlight how we envision a new phase for mouse systems genetics in evolut
 ionary and biomedical areas.
LOCATION:CRUK CI Room 009/009A
END:VEVENT
END:VCALENDAR