NDLI: Intergenic variants of HBS1L-MYB are responsible for a major quantitative trait locus on chromosome 6q23 influencing fetal hemoglobin levels in adults

Content Provider	PubMed Central
Author	Thein, Swee Lay Menzel, Stephan Peng, Xu Best, Steve Jiang, Jie Close, James Silver, Nicholas Gerovasilli, Ageliki Ping, Chen Yamaguchi, Masao Wahlberg, Karin Pinar, Ulug Spector, Tim D. Garner, Chad Matsuda, Fumihiko Farrall, Martin Lathrop, Mark
Copyright Year	2007
Abstract	Individual variation in fetal hemoglobin (HbF, α2γ2) response underlies the remarkable diversity in phenotypic severity of sickle cell disease and β thalassemia. HbF levels and HbF-associated quantitative traits (e.g., F cell levels) are highly heritable. We have previously mapped a major quantitative trait locus (QTL) controlling F cell levels in an extended Asian-Indian kindred with β thalassemia to a 1.5-Mb interval on chromosome 6q23, but the causative gene(s) are not known. The QTL encompasses several genes including HBS1L, a member of the GTP-binding protein family that is expressed in erythroid progenitor cells. In this high-resolution association study, we have identified multiple genetic variants within and 5′ to HBS1L at 6q23 that are strongly associated with F cell levels in families of Northern European ancestry (P = 10−75). The region accounts for 17.6% of the F cell variance in northern Europeans. Although mRNA levels of HBS1L and MYB in erythroid precursors grown in vitro are positively correlated, only HBS1L expression correlates with high F cell alleles. The results support a key role for the HBS1L-related genetic variants in HbF control and illustrate the biological complexity of the mechanism of 6q QTL as a modifier of fetal hemoglobin levels in the β hemoglobinopathies.
Related Links	http://dx.doi.org/10.1073/pnas.0611393104
Starting Page	11346
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	27
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-07-03
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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