title: Quantitative trait locus on chromosome 8q influences the switch from fetal to adult hemoglobin.
abstract: The switch from fetal to adult hemoglobin is incomplete; the residual fetal hemoglobin in adults is restricted to a subset of erythrocytes called F cells. F-cell levels are influenced by a sequence variant (C-->T) at position -158 upstream of the gamma-globin gene, termed the XmnI-Ggamma polymorphism. How the Ggamma-158 C-->T variant influences the expression of the Ggamma-globin gene is unknown but is likely to involve the interaction of a multiprotein transcription complex. In a recent genome-wide linkage study of a large Asian Indian kindred, a genetic interaction between the XmnI-Ggamma site and a locus on chromosome 8q was reported to influence adult F-cell levels. We report the replication of linkage to chromosome 8q in a sample of European twin pairs. This result provides strong evidence that a quantitative trait locus exists on chromosome 8q that influences the developmental switch from fetal to adult hemoglobin.
authors.affiliation: Epidemiology Division, Department of Medicine, University of California Irvine, Irvine, CA 92697-7550, USA. cgarner@uci.edu
authors.forename: Chad
authors.initials: C
authors.lastname: Garner
authors.forename: Nicholas
authors.initials: N
authors.lastname: Silver
authors.forename: Steve
authors.initials: S
authors.lastname: Best
authors.forename: Stephan
authors.initials: S
authors.lastname: Menzel
authors.forename: Charlotte
authors.initials: C
authors.lastname: Martin
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Swee Lay
authors.initials: SL
authors.lastname: Thein
mesh_terms: D000328:Adult; D000368:Aged; D002898:Chromosomes, Human, Pair 8; D004912:Erythrocytes / Q000378:metabolism; D005060:Europe; D005260:Female; D005319:Fetal Hemoglobin / Q000737:chemistry / Q000235:genetics*; D008040:Genetic Linkage; D016678:Genome; D005838:Genotype; D006454:Hemoglobins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010641:Phenotype; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci
chemical_list: D006454:Hemoglobins; D005319:Fetal Hemoglobin