A family with haemolytic anaemia and three beta-globins: the deletion in haemoglobin Atlanta-Coventry (beta 75 Leu----Pro, 141 Leu deleted) is not present at the nucleotide level.
Analyses of haemoglobin from a family with an unstable haemoglobin haemolytic anaemia demonstrated that the affected individuals had three beta-globins, namely, normal (beta A), Atlanta (beta At) with a mutation of beta 75 Leu----Pro, and beta-Atlanta-Coventry (beta At-Co) with mutation of beta 75 Leu----Pro and beta 141 Leu deleted. These were present in the ratio 66:23:11 respectively. The structure of the beta-globin cluster, however, was found to be normal by Southern blotting; also cytogenetic analysis failed to show any abnormality. DNA sequence analyses demonstrated the presence of the beta At mutation in genomic DNA isolated from leucocytes but the Coventry deletion of 141 Leu in beta At-Co was not present in genomic DNA. PCR amplification of the beta-globin cDNA and direct sequencing of the product also failed to demonstrate the Coventry deletion. Thus, it appears that the absence of 141 Leu in the beta At-Co globin is a consequence of the beta At mutation in these patients and that both beta At and beta At-Co are the product of a single gene. This unusual conclusion is paralleled in the bizarre case of Hb Vicksburg where the deletion of a leucine at beta 75 is not coded for in genomic DNA.
George
P M
PM
Molecular Pathology Laboratory, Christchurch Hospital, New Zealand.
Myles
T
T
Williamson
D
D
Higuchi
R
R
Symmans
W A
WA
Brennan
S O
SO
D000743:Anemia, Hemolytic / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D002872:Chromosome Deletion; D003062:Codon / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D005914:Globins / Q000032:analysis / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000032:analysis*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011392:Proline / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
D003062:Codon; D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; D005914:Globins; D004247:DNA; C076820:hemoglobin Atlanta-Coventry; D011392:Proline; D007930:Leucine