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Analysis of Haemophilia B Database and Strategies for Identification of Common point Mutations in the Factor IX Gene

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Title Analysis of Haemophilia B Database and Strategies for
Identification of Common point Mutations in the Factor IX
Gene
 
Creator Mukherjee, S
Mukhopadhyay, A
Chaudhuri, Keya
Ray, Kunal
 
Subject Infectious Diseases and Immunology
 
Description Haemophilia B is an X-linked recessively
inherited bleeding disorder caused by heterogeneous
mutations spanning the entire factor IX gene. As
spontaneous germ-line mutations are known to occur
mostly at CpG dinucleotides in the FIX gene, control
of the disease would require continuous carrier
detection and mutation screening. Identification of
point mutations, the most common type of mutation
in FIX gene, is more challenging compared with
deletion and insertion mutations. We examined the
haemophilia B database to identify specific nucleotides
in the FIX gene that are mutated in relatively
large number of patients and the variability (if any)
in the mutational hotspots at CpG dinucleotides. It
was found that while mutations responsible to
account for all 2348 haemophilia B patients covered
20% of the FIX cDNA, only 1% of the cDNA
involving mostly CpG dinucleotides accounted for
mutation in 42.41% of the patient pool. Thus, only
27 nucleotides need to be investigated to identify the
common point mutations, among which 15 are
predicted to undergo change in restriction sites on
mutation. It is interesting to note that seven nucleotides
occurring in CpG dinucleotides do not have
any reported mutation despite each of those being
predicted to harbour mutation as a result of transition
and having mutations recorded in the database
for the neighbouring nucleotides. Strikingly large
number of mutation in codon 296 causing T to M
change in catalytic domain originally proposed to be
the result of the founder effect also contains largest
number of haplotype suggesting recurrence of
de novo mutation. Keywords: bleeding disorder, CpG, database, factor IX, haemophilia, mutation
 
Date 2003
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/944/1/HAEMOPHILIA%2C_9(_2)_187%2D192[76].pdf
Mukherjee, S and Mukhopadhyay, A and Chaudhuri, Keya and Ray, Kunal (2003) Analysis of Haemophilia B Database and Strategies for Identification of Common point Mutations in the Factor IX Gene. Haemophilia, 9 (2). pp. 187-192.
 
Relation http://dx.doi.org/10.1046/j.1365-2516.2003.00727.x
http://www.eprints.iicb.res.in/944/