The Malmo polymorphism of factor IX: establishing the genotypes by rapid
analysis of DNA
JB Graham, GR Kunkel, GS Tennyson, ST Lord and DM Fowlkes
Department of Pathology, School of Medicine, University of North Carolina,
Chapel Hill 27599.
A DNA polymorphism in the coding region of coagulation factor IX--
potentially valuable for carrier detection, prenatal diagnosis, and
population studies--was described in 1985. It had been discovered with
monoclonal antibodies that distinguish between threonine and alanine as the
148th residue of the peptide. Its use as a diagnostic tool has been limited
because threonine-containing factor IX (Malmo A) is dominant to
alanine-containing factor IX (Malmo B) in immunoassays of plasma;
therefore, detection of Malmo heterozygotes is not possible in all
instances. A DNA method for recognizing all heterozygotes has been
developed, but it also has limitations. We report the development of
another DNA procedure based on amplification of the relevant DNA with the
polymerase chain reaction (PCR). This method is quick, avoids the use of
isotopes and x-ray film, and specifically identifies all the Malmo
genotypes: hemizygotes, homozygotes, and heterozygotes. The procedure can
be performed satisfactorily on small samples of blood (less than 1 mL) as
suggested by Kogan et al (N Engl J Med 317:985, 1987). The method described
is applicable to any genetic polymorphism that overlaps a restriction
enzyme recognition site.
Volume 73,
Issue 8,
pp. 2104-2107,
06/01/1989
Copyright © 1989 by The American Society of Hematology
