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SUMMARY:The evolutionary dynamics and fitness landscape of clones in our b
 lood - Jamie Blundell\, University of Cambridge
DTSTART:20191101T160000Z
DTEND:20191101T170000Z
UID:TALK132538@talks.cam.ac.uk
CONTACT:Diana Fusco
DESCRIPTION:Somatic mutations acquired in healthy tissues as we age are ma
 jor determinants of cancer risk. Whether variants confer a fitness advanta
 ge or rise to detectable frequencies by chance\, however\, remains largely
  unknown. Here\, by combining blood sequencing data from ∼50\,000 indivi
 duals and mathematical models borrowed from statistical physics\, we revea
 l how mutation\, genetic drift and fitness differences combine to shape th
 e genetic diversity of healthy blood (‘clonal haematopoiesis’). By ana
 lysing the spectrum of variant allele frequencies we quantify fitness adva
 ntages for key pathogenic variants and genes and provide bounds on the num
 ber of haematopoietic stem cells. Positive selection\, not drift\, is the 
 major force shaping clonal haematopoiesis. The remarkably wide variation i
 n variant allele frequencies observed across individuals is driven by chan
 ce differences in the timing of mutation acquisition combined with differe
 nces in the cell-intrinsic fitness effect of variants. \n\nI then go on to
  describe on-going work in our lab where we exploit serial blood samples (
 collected from the same individuals each year over decade-long timescales)
  to watch the genetic evolution that leads to blood cancers and how this d
 iffers from the evolution that occurs in cancer-free individuals. We find 
 that some of the key mutations driving blood cancers occur >10 years befor
 e cancer diagnosis which opens up the possibility of using these as "bellw
 ethers" for early detection and intervention.  
LOCATION: Small Lecture Theatre\, Cavendish Laboratory\, J.J. Thomson Aven
 ue
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