HAPLOTYPE MAPPING OF A MAJOR QUANTITATIVE-TRAIT LOCUS FOR FETAL HEMOGLOBIN PRODUCTION, ON CHROMOSOME 6Q23

Fetal hemoglobin (Hb F) and fetal cell (FC) levels in adults show cons iderable variation and are influenced by several genetic variants; the major determinants appear to be unlinked to the beta-globin gene clus ter. Recently, a trans-acting locus controlling Hb F and FC production has been mapped to chromosome 6q23 in an Asian Indian kindred that in cludes individuals with heterocellular hereditary persistence oi: 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 l inkage of the quantitative-trait locus (QTL) to the anonymous markers D6S976 (LOD score 11.3; recombination fraction .00) and D6S270 (LOD sc ore 7.4; recombination fraction .00). Key recombination events now pla ce this QTL within a 1-2-cM interval spanning similar to 1.5 Mb betwee n D6S270 and D6S1626. Furthermore, haplotype analysis has led to a ree valuation of the genealogy and to the identification of additional rel ationships in the kindred.