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Informativeness of linkage analysis for genetic diagnosis of haemophilia A in India
Author(s) -
Jayandharan G.,
Shaji R. V.,
George B.,
Chandy M.,
Srivastava A.
Publication year - 2004
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2004.00908.x
Subject(s) - intron , genetics , allele , haemophilia a , biology , gene , microbiology and biotechnology , haemophilia
Summary. The objective of this study was to assess the frequency of factor VIII (FVIII) gene intron 1 and intron 22 inversions and the informativeness of polymorphic markers for the genetic diagnosis of patients with haemophilia A (HA). Fifty unrelated patients with HA were first assessed for the intron 1 and intron 22 inversion mutations. Inversion‐negative families were then screened for the bi‐allelic intragenic markers – intron 7 G→A polymorphism, Hin dIII site in intron 19 and Xba I site in intron 22 and the multiallelic dinucleotide CA repeat alleles in introns 13 and 22. The extragenic, multiallelic VNTR DXS 52 (st14) was also analysed. Intron 22 inversion mutation was found in 38% ( n = 19) of all patients and 46% of those with severe HA. Intron 1 inversion was found in one (2%) patient. Of the 30 inversion‐negative families, Xba I site polymorphism was the single most informative marker (70%, n = 21/30) followed by Hin dIII (60%, n = 18/30), intron 13 CA repeats (56.66%, n = 17/30), intron 22 CA repeats (50%, n = 15/30), DXS 52 VNTR (23.33%, n = 7/30) and intron 7 G→A polymorphism (6.66%, n = 2/30). The combined use of these markers was informative in 92% ( n = 46/50) of HA families. Based on the informativeness of these markers a comprehensive algorithm has been proposed for genetic diagnosis of HA in India.