title: Haplotype mapping of a major quantitative-trait locus for fetal hemoglobin production, on chromosome 6q23.
abstract: Fetal hemoglobin (Hb F) and fetal cell (FC) levels in adults show considerable variation and are influenced by several genetic variants; the major determinants appear to be unlinked to the beta-globin gene cluster. Recently, a trans-acting locus controlling Hb F and FC production has been mapped to chromosome 6q23 in an Asian Indian kindred that includes individuals with heterocellular hereditary persistence of Hb F (HPFH) associated with beta thalassemia. We have extended the kindred by 57 members, bringing the total studied to 210, and have saturated the region with 26 additional markers. Linkage analysis showed tight linkage of the quantitative-trait locus (QTL) to the anonymous markers D6S976 (LOD score 11.3; recombination fraction .00) and D6S270 (LOD score 7.4; recombination fraction .00). Key recombination events now place this QTL within a 1-2-cM interval spanning approximately 1.5 Mb between D6S270 and D6S1626. Furthermore, haplotype analysis has led to a reevaluation of the genealogy and to the identification of additional relationships in the kindred.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Garner
authors.forename: J
authors.initials: J
authors.lastname: Mitchell
authors.forename: T
authors.initials: T
authors.lastname: Hatzis
authors.forename: J
authors.initials: J
authors.lastname: Reittie
authors.forename: M
authors.initials: M
authors.lastname: Farrall
authors.forename: S L
authors.initials: SL
authors.lastname: Thein
mesh_terms: D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D005260:Female; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics*; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D019655:Quantitative Trait, Heritable
chemical_list: D005319:Fetal Hemoglobin