Linkage of alpha G-Philadelphia to alpha-thalassemia in African-Americans .
We have studied the inheritance of the alpha-chain hemoglobin variant Hb G-Philadelphia (alpha 2(68 Asn leads to Lys)Beta 2) in two African-American families. Expression of the alpha-globin loci was monitored by the percentage of Hb G in these individuals. The variant represented approximately 33% of the total adult hemoglobin in some and 50% in others. alpha-Globin gene fragments were analyzed by using restricton endonucleases that cleave outside (EcoRI), within (HindIII), and between (Bgl II) the normal duplicated alpha-globin loci (alpha alpha/alpha alpha). Individuals having 33% variant lack one functioning alpha gene (alpha G/alpha alpha); those with 50% variant lack two genes, one missing on each chromosome (alpha G/alpha). Inheritance of alpha G was therefore linked to that of a chromosome with only one functional alpha-globin gene locus. This locus is probably the result of a nonhomologous crossover. Our results also suggest equal expression of the alpha-globin loci in humans because the percentages of the variant could be explained solely on the basis of the total number of alpha genes present. The percentages of Hb G as well as other hematologic data all were consistent with the number of alpha-globin genes identified by restriction endonuclease mapping. Gene mapping yields a more precise determination of the number of alpha-globin genes than does study of globin synthesis.
D000349:Africa / Q000208:ethnology; D044383:Black People; D002872:Chromosome Deletion; D005796:Genes; D008040:Genetic Linkage; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D013789:Thalassemia / Q000235:genetics*; D001741:Black or African American
D006455:Hemoglobins, Abnormal; D005914:Globins