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Hemophilia A: genetic prediction and linkage studies in all available families in Finland
Author(s) -
Lehesjoki AnnaElina,
Sistonen Pertti,
Rasi Vesa,
Chapelle Albert
Publication year - 1991
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1991.tb03012.x
Subject(s) - genetic linkage , lod score , restriction fragment length polymorphism , genetics , genetic marker , linkage (software) , population , prenatal diagnosis , biology , bglii , gene mapping , gene , medicine , genotype , restriction enzyme , pregnancy , hindiii , fetus , environmental health , chromosome
RFLP studies were done in 82 (75%) of all known hemophilia A families in the Finnish population (approximately 5 million). Two intragenic RFLPs (BcII/F8A, Xbal/p482.6) and two extragenic markers (Taql/St14, BglII/DX13) were used. Among 263 females at risk, carriership could be evaluated with an intragenic marker in 47% and with an extragenic marker in 26%. In 27% of the females, carriership could be neither excluded nor confirmed; 68% of these females were relatives of an isolated patient. Eight recombinations between the factor VIII gene (F8C) and DXS52 (lod 25.02 at θ max 0.06), eight recombinations between F8C and DXS15 (lod 21.91 at θ max 0.05), and two recombinations between DXS52 and DXS15 (lod 33.56 at θ max 0.01) were found. Using multipoint linkage analysis, the most likely order of loci supported by the data was: F8C‐DXS15‐DXS52‐DXS134. RFLP segregation analysis provides a highly useful method of carrier detection and prenatal diagnosis of hemophilia A, but its limitations must be carefully taken into account.