Related Experiment Video
Updated: May 25, 2026

An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
Published on: November 3, 2010
DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status
Karin Weiner Lachmi1, Ling Lin, Birgitte Rahbek Kornum
1Center for Sleep Sciences, Stanford University, Palo Alto, CA 94304-5592, USA.
Abstract:
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.
Related Concept Videos
Genetic Lingo
Sleep-Wake Cycles
NREM Sleep
NREM sleep comprises four progressive stages that seamlessly merge:
Narcolepsy
Dosage Compensation
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
Epistasis Analysis
Circadian Rhythms and Gene Regulation

