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Genetic Variation on Chromosome 6 Influences F Cell Levels in Healthy Individuals of African Descent and HbF Levels in Sickle Cell Patients

Authors: Creary, LE; Ulug, P; Menzel, S; McKenzie, CA; Hanchard, NA; Taylor, V; Farrall, M; +2 Authors

Genetic Variation on Chromosome 6 Influences F Cell Levels in Healthy Individuals of African Descent and HbF Levels in Sickle Cell Patients

Abstract

Fetal haemoglobin (HbF) is a major ameliorating factor in sickle cell disease. We investigated if a quantitative trait locus on chromosome 6q23 was significantly associated with HbF and F cell levels in individuals of African descent. Single nucleotide polymorphisms (SNPs) in a 24-kb intergenic region, 33-kb upstream of the HBS1L gene and 80-kb upstream of the MYB gene, were typed in 177 healthy Afro-Caribbean subjects (AC) of approximately 7% European admixture, 631 healthy Afro-Germans (AG, a group of African and German descendents located in rural Jamaica with about 20% European admixture), 87 West African and Afro-Caribbean individuals with sickle cell anaemia (HbSS), as well as 75 Northern Europeans, which served as a contrasting population. Association with a tag SNP for the locus was detected in all four groups (AC, P = 0.005, AG, P = 0.002, HbSS patients, P = 0.019, Europeans, P = 1.5 x 10(-7)). The association signal varied across the interval in the African-descended groups, while it is more uniform in Europeans. The 6q QTL for HbF traits is present in populations of African origin and is also acting in sickle cell anaemia patients. We have started to distinguish effects originating from European and African ancestral populations in our admixed study populations.

Country
United Kingdom
Keywords

570, General Science & Technology, Science, European Continental Ancestry Group, 610, Black People, Anemia, Sickle Cell, Polymorphism, Single Nucleotide, Chromosomes, White People, Tropical medicine, MD Multidisciplinary, Humans, Polymorphism, Fetal Hemoglobin, African Continental Ancestry Group, Science & Technology, Genetics (medical sciences), Q, R, Genetic Variation, Anemia, Single Nucleotide, Sickle Cell, Multidisciplinary Sciences, Science & Technology - Other Topics, Medicine, Chromosomes, Human, Pair 6, Pair 6, Haematology, Human, Research Article

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
76
Top 10%
Top 10%
Top 10%
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gold