Human blood genomics: distinct profiles for gender, age and neurofibromatosis type 1.
Application of gene expression profiling to human diseases will be limited by availability of tissue samples. It was postulated that germline genetic defects affect blood cells to produce unique expression patterns. This hypothesis was addressed by using a test neurological disease-neurofibromatosis type 1 (NF1), an autosomal dominant genetic disease caused by mutations of the NF1 gene at chromosome 17q11.2. Oligonucleotide arrays were used to survey the blood gene expression pattern of 12 NF1 patients compared to 96 controls. A group of genes related to tissue remodeling, bone development and tumor suppression were down-regulated in NF1 blood samples. In addition, there were blood genomic patterns for gender and age: Y chromosome genes showing higher expression in males, indicating a gene-dosage effect; and genes related to lymphocyte functions showing higher expression in children. The results suggest that genetic mutations can be manifested at the transcriptional level in peripheral blood cells and blood gene expression profiling may be useful for studying phenotypic differences of human genetic diseases and possibly providing diagnostic and prognostic markers.
Tang
Yang
Y
Department of Neurology, University of Cincinnati, Vontz Center, Room 2327, 3125 Eden Avenue, Cincinnati, OH 45267-0536, USA.
Lu
Aigang
A
Ran
Ruiqiong
R
Aronow
Bruce J
BJ
Schorry
Elizabeth K
EK
Hopkin
Robert J
RJ
Gilbert
Donald L
DL
Glauser
Tracy A
TA
Hershey
Andrew D
AD
Richtand
Neil W
NW
Privitera
Michael
M
Dalvi
Arif
A
Sahay
Alok
A
Szaflarski
Jerzy P
JP
Ficker
David M
DM
Ratner
Nancy
N
Sharp
Frank R
FR
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001790:Blood Physiological Phenomena; D005260:Female; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000097:blood* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors