DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status
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DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status. / Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek; Rico, Tom; Lo, Betty; Aran, Adi; Mignot, Emmanuel.
In: Human Immunology, Vol. 73, No. 4, 04.2012, p. 405-10.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status
AU - Weiner Lachmi, Karin
AU - Lin, Ling
AU - Kornum, Birgitte Rahbek
AU - Rico, Tom
AU - Lo, Betty
AU - Aran, Adi
AU - Mignot, Emmanuel
N1 - Copyright © 2012 American Society for Histocompatibility and Immunogenetics. All rights reserved.
PY - 2012/4
Y1 - 2012/4
N2 - The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression in peripheral white blood cells of 50 narcolepsy versus 47 controls (half of whom were DQB1*06:02 positive) and observed the largest differences between the groups in the signal from HLA probes. Further studies of HLA-DQ expression (mRNA and protein in a subset) in 125 controls and 147 narcolepsy cases did not reveal any difference, a result we explain by the lack of proper control of allelic diversity in Affymetrix HLA probes. Rather, a clear effect of DQB1*06:02 allelic dosage on DQB1*06:02 mRNA levels (1.65-fold) and protein (1.59-fold) could be demonstrated independent of disease status. These results indicate that allelic dosage is transmitted into changes in heterodimer availability, a phenomenon that may explain the increased risk for narcolepsy in DQB1*06:02 homozygotes versus heterozygotes.
AB - The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression in peripheral white blood cells of 50 narcolepsy versus 47 controls (half of whom were DQB1*06:02 positive) and observed the largest differences between the groups in the signal from HLA probes. Further studies of HLA-DQ expression (mRNA and protein in a subset) in 125 controls and 147 narcolepsy cases did not reveal any difference, a result we explain by the lack of proper control of allelic diversity in Affymetrix HLA probes. Rather, a clear effect of DQB1*06:02 allelic dosage on DQB1*06:02 mRNA levels (1.65-fold) and protein (1.59-fold) could be demonstrated independent of disease status. These results indicate that allelic dosage is transmitted into changes in heterodimer availability, a phenomenon that may explain the increased risk for narcolepsy in DQB1*06:02 homozygotes versus heterozygotes.
KW - Adult
KW - Alleles
KW - B-Lymphocytes/immunology
KW - Case-Control Studies
KW - Female
KW - Gene Dosage
KW - Gene Expression
KW - Gene Expression Profiling
KW - Genotype
KW - HLA-DQ beta-Chains/genetics
KW - Humans
KW - Male
KW - Narcolepsy/genetics
U2 - 10.1016/j.humimm.2012.01.004
DO - 10.1016/j.humimm.2012.01.004
M3 - Journal article
C2 - 22326585
VL - 73
SP - 405
EP - 410
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 4
ER -
ID: 196168806