title: Evidence of genetic interaction between the beta-globin complex and chromosome 8q in the expression of fetal hemoglobin.
abstract: During human development, the switch from fetal to adult hemoglobin (Hb) is not complete with the residual gamma-globin expression being restricted to a subset of erythrocytes termed "F cells" (FC). Statistical analyses have shown the FC trait to be influenced by a common sequence variant (C-->T) at position -158 upstream of the Ggamma-globin gene, termed the "XmnI-Ggamma polymorphism." The XmnI-Ggamma site is believed to be involved in the expression of the Ggamma-globin gene through interaction with transcription factors, and polymorphisms in the transcription factors could be influencing fetal Hb expression, conditional on the XmnI-Ggamma site. Using a two-locus model, in which the second locus was the known quantitative-trait locus (QTL) at the XmnI-Ggamma site, we showed suggestive linkage to chromosome 8q. A maximum single-point LOD score of 4.33 and a multipoint LOD score of 4.75 were found in a 15-20 cM region of chromosome 8q. A single-locus analysis failed to show linkage of FC to the region when the XmnI-Ggamma site was accounted for by removing its effects from the data or including it as a covariate. Results of the single-locus analysis were significant when the effects of the XmnI-Ggamma site were not accounted for in any way. The results of analysis in a large Indian kindred indicate that there is an interaction between the XmnI-Ggamma site and a QTL on chromosome 8q that is influencing the production of fetal Hb.
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720-3140, USA. cgarner@socrates.berkeley.edu
authors.forename: Chad P
authors.initials: CP
authors.lastname: Garner
authors.forename: Thanusak
authors.initials: T
authors.lastname: Tatu
authors.forename: Steve
authors.initials: S
authors.lastname: Best
authors.forename: Lisa
authors.initials: L
authors.lastname: Creary
authors.forename: Swee Lay
authors.initials: SL
authors.lastname: Thein
mesh_terms: D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005319:Fetal Hemoglobin / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008957:Models, Genetic; D011336:Probability; D019655:Quantitative Trait, Heritable
chemical_list: D005819:Genetic Markers; D005914:Globins; D005319:Fetal Hemoglobin