Premium
Hemoglobin constant spring defined by specific oligonucleotide hybridization and hemoglobin D Punjab (β 121 → Gln ) in a Batak Indonesian family
Author(s) -
Kosasih Eddi N.,
Cai ShiPing,
Kan Yuet W.,
LieInjo Luan Eng
Publication year - 1988
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830290106
Subject(s) - fetal hemoglobin , hemoglobin , microbiology and biotechnology , genetics , oligonucleotide , oligomer restriction , hemoglobin variants , globin , hemoglobinopathy , gene , biology , stop codon , hemolytic anemia , fetus , biochemistry , immunology , pregnancy
A Batak Indonesian from North Sumatra with hemoglobin (Hb) D Punjab (α 2 β 2 121 → Gln ) and hemoglobin Constant Spring (Hb CoSp) is described. The 24‐year‐old man did not have clinical symptoms, and his hematological indices were normal. However, he had a persistent slight elevation of fetal hemoglobin level. His mother and his brother were heterozygous for Hb D Punjab; his father had Hb CoSp trait. A sister did not have any abnormal hemoglobin. To show the exact molecular defect leading to the synthesis of Hb CoSp in this family, genomic DNA from the father was analyzed by hybridization with synthetic oligonucleotides. Genomic DNA was digested with Sst I and Hind III producing a 1.05‐kb fragment from the 3′ end segment of the α 2 ‐globin gene, including the termination codon. Two nonadecamers were synthesized to serve as probes: one, entirely homologous to the normal 3′ end of α 2 A ‐globin gene sequence, including the termination codon TAA, the other different from it by a replacement of the T in the termination codon TAA with C, changing it to CAA, the codon for the amino acid glutamine. DNA from normal controls gave a positive signal with the normal α 2 TAA oligonucleotide probe but negative with the α 2 CAA probe. The father of propositus who had Hb CoSp trait gave a positive signal with the normal α 2 TAA oligonucleotide probe as well as with the α 2 CAA oligonucleotide probe, showing him to be heterozygous for the α 2 CAA ‐globin gene. This result shows that the Hb CoSp in the Batak family is indeed due to a replacement of T by C in the TAA termination codon of the α 2 ‐globin gene changing it to CAA the codon for glutamine. This explains the resulting readthrough of the untranslated sequence of the mRNA.