PMID: 2105906Jan 1, 1990Paper

Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA

Genomics
M HiguchiS E Antonarakis

Abstract

In order to search for mutations resulting in hemophilia A that are not detectable by restriction analysis, three regions of the factor VIII gene were chosen for direct sequence analysis. Short segments of genomic DNA of 127 unrelated patients with hemophilia A were amplified by polymerase chain reaction. A total of 136,017 nucleotides were sequenced, and four mutations leading to the disease were found: a frameshift at codon 360 due to deletion of two nucleotides (GA), a nonsense codon 1705 due to a C----T transition, and two missense codons at positions 1699 and 1708. The first missense mutation (A----T) results in a Tyr----Phe substitution at a putative von Willebrand factor binding site. The second results in an Arg----Cys substitution at a thrombin cleavage site. In addition, we identified three rare sequence variants: a silent C----T transition at codon 34 which does not result in an amino acid change, a G----C change at codon 345 (Val----Leu), and an A----G change at the third nucleotide of intron 14. Direct sequence analysis of amplified DNA is a powerful but labor-intensive method of identifying mutations in large genes such as the human factor VIII gene.

References

Jun 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M AraiL W Hoyer
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·V C SheffieldR M Myers
Nov 1, 1988·Human Genetics·S E AntonarakisS K Karathanasis
Jan 1, 1985·Human Genetics·D N CooperJ Schmidtke
Oct 3, 1985·The New England Journal of Medicine·S E AntonarakisD N Fass
Jun 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·H YoussoufianH H Kazazian
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D D Pittman, R J Kaufman
May 1, 1988·Archives of Biochemistry and Biophysics·P J Fay
Aug 1, 1988·Trends in Genetics : TIG·S E Antonarakis, H H Kazazian
Jun 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R G CottonR D Campbell
Apr 7, 1988·Nature·R HiguchiH A Erlich
May 2, 1986·Science·R M MyersT Maniatis
Oct 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·A ChakravartiP H Seeburg
Nov 22, 1984·Nature·J GitschierR M Lawn
Nov 22, 1984·Nature·G A VeharD J Capon
Oct 1, 1980·Cell·A EfstratiadisN J Proudfoot

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Citations

Oct 13, 2006·Nature Biotechnology·Gary Walsh, Roy Jefferis
Sep 1, 1995·Nature Structural Biology·Y PanF E Cohen
Aug 25, 1991·Proceedings of the National Academy of Sciences of the United States of America·M HiguchiS E Antonarakis
Oct 11, 1991·Proceedings of the National Academy of Sciences of the United States of America·M HiguchiH H Kazazian
Jun 11, 1992·Proceedings of the National Academy of Sciences of the United States of America·A M AlyL W Hoyer
Jan 1, 1991·Annals of the New York Academy of Sciences·J Gitschier
Feb 12, 2002·Molecular Pathology : MP·D J Bowen
Apr 16, 2002·Molecular Pathology : MP·D J Bowen
Mar 13, 2012·Experimental Eye Research·Yogita KananMuayyad R Al-Ubaidi
Jul 1, 1991·Transfusion Medicine Reviews·D Lillicrap
Oct 26, 2007·Journal of Thrombosis and Haemostasis : JTH·M van den BiggelaarK Mertens
Sep 29, 2011·Haemophilia : the Official Journal of the World Federation of Hemophilia·A GringeriA B Federici
Jun 16, 2009·Experimental Eye Research·Yogita KananMuayyad R Al-Ubaidi
Sep 1, 2005·Journal of Thrombosis and Haemostasis : JTH·K Hansson, J Stenflo
Jul 1, 2014·Haemophilia : the Official Journal of the World Federation of Hemophilia·P M MannucciR Klamroth
Jan 1, 1995·Human Mutation·S E AntonarakisE G Tuddenham
Jan 15, 1992·American Journal of Medical Genetics·D P ZhuI H Maumenee
Jun 3, 2005·Nature Reviews. Genetics·Jochen GrawRainer Schwaab
Nov 6, 2001·The Journal of Biological Chemistry·Aurea D Sousa, Chuck S Farah
Jan 5, 1999·Haemophilia : the Official Journal of the World Federation of Hemophilia·S E Antonarakis
May 6, 2003·The Journal of Biological Chemistry·Kevin L Moore
Nov 7, 2008·The Biochemical Journal·Zsolt RónaiMiklós Sahin-Tóth

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