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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Aging+Cell
2013 ; 12
(2
): 269-79
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gab.com Text
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Large chromosome deletions, duplications, and gene conversion events accumulate
with age in normal human colon crypts
#MMPMID23425690
Hsieh JC
; Van Den Berg D
; Kang H
; Hsieh CL
; Lieber MR
Aging Cell
2013[Apr]; 12
(2
): 269-79
PMID23425690
show ga
Little is known about the types and numbers of mutations that may accumulate in
normal human cells with age. Such information would require obtaining enough DNA
from a single cell to accurately carry out reliable analysis despite extensive
amplification; and complete genomic coverage under these circumstances is
difficult. We have compared colon crypts, which are putatively clonal and contain
~2000 cells each, to determine how much somatic genetic variation occurs in vivo
(without ex vivo cell culturing). Using high-density SNP microarrays, we find
that chromosome deletions, duplications, and gene conversions were significantly
more frequent in colons from the older individuals. These changes affected
lengths ranging from 73 kb to 46 Mb. Although detection requires progeny of a
single mutant stem cell to reach niche dominance over neighboring stem cells,
none of the deletions appear likely to confer a selective advantage. Mutations
can become fixed randomly during stem cell evolution through neutral drift in
normal human crypts. The fact that chromosomal changes are detected in individual
crypts with increasing age suggests that either such changes accumulate with age
or single stem cell dominance increases with age, and the former is more likely.
This progressive genome-wide divergence of human somatic cells with age has
implications for aging and disease in multicellular organisms.