Evaluation of allelic expression of imprinted genes in adult human blood.
BACKGROUND
Imprinted genes are expressed from only one allele in a parent-of-origin dependent manner. Loss of imprinted (LOI) expression can result in a variety of human disorders and is frequently reported in cancer. Biallelic expression of imprinted genes in adult blood has been suggested as a useful biomarker and is currently being investigated in colorectal cancer. In general, the expression profiles of imprinted genes are well characterised during human and mouse fetal development, but not in human adults.


RESULTS
We investigated quantitative expression of 36 imprinted genes in adult human peripheral blood leukocytes obtained from healthy individuals. Allelic expression was also investigated in B and T lymphocytes and myeloid cells. We found that 21 genes were essentially undetectable in adult blood. Only six genes were demonstrably monoallelic, and most importantly, we found that nine genes were either biallelic or showed variable expression in different individuals. Separated leukocyte populations showed the same expression patterns as whole blood. Differential methylation at each of the imprinting control loci analysed was maintained, including regions that contained biallelically expressed genes. This suggests in some cases methylation has become uncoupled from its role in regulating gene expression.


CONCLUSIONS
We conclude that only a limited set of imprinted genes, including IGF2 and SNRPN, may be useful for LOI cancer biomarker studies. In addition, blood is not a good tissue to use for the discovery of new imprinted genes. Finally, lymphocyte DNA methylation status in the adult may not always be a reliable indicator of monoallelic gene expression.
Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, United Kingdom. j.frost@ich.ucl.ac.uk
Jennifer M
JM
Frost
Dave
D
Monk
Taita
T
Stojilkovic-Mikic
Kathryn
K
Woodfine
Lyn S
LS
Chitty
Adele
A
Murrell
Philip
P
Stanier
Gudrun E
GE
Moore
D000328:Adult; D000483:Alleles; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction