Quantitative trait locus on chromosome 8q influences the switch from fetal to adult hemoglobin

Abstract

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 γ-globin gene, termed the XmnI-Gγ polymorphism. How the Gγ-158 C → T variant influences the expression of the Gγ-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-Gγ 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. (Blood. 2004;104:2184-2186)