Molecular Diagnosis of Wilson Disease Using Prevalent Mutations and Informative Single- Nucleotide Polymorphism Markers
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Molecular Diagnosis of Wilson Disease Using Prevalent Mutations and Informative Single- Nucleotide Polymorphism Markers
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| Creator |
Gupta, Arnab
Maulik, Mahua Nasipuri, Poonam Chattopadhyay, Ishita Das, Shyamal K Gangopadhyay, Prasanta K Ray, Kunal |
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| Subject |
Molecular & Human Genetics
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| Description |
Wilson disease (WD) is an autosomal
recessive disorder caused by defects in the ATPase,
Cu2� transporting, �-polypeptide gene (ATP7B) resulting
in accumulation of copper in liver and brain. WD
can be thwarted if detected at a presymptomatic stage,
but occasional recombination during carrier detection
with dinucleotide repeat markers flanking the WD
locus may lead to faulty diagnosis. We examined the use
of intragenic single-nucleotide polymorphism (SNP)
markers to avoid this limitation. We prepared genomic DNA from the peripheral
blood of Indian WD patients. By use of PCR, we
amplified the exons and flanking regions of the WD
gene and then performed sequencing to identify the
nucleotide variants. We genotyped the SNPs in 1871
individuals by use of the Sequenom mass array system.
We made linkage disequilibrium plots using Haploview
software.
We identified 1 mutation accounting for 11%
(19 of 174) of WD chromosomes among patients in
addition to 4 prevalent mutations characterized previously.
Among 24 innocuous allelic variants identified,
we selected 3 SNPs found to have high heterozygosity (>0.40) for the detection of mutant WD chromosomes.
On analyzing these SNPs in 28 test individuals, who
were sibs to 17 unrelated WD patients, we obtained
unequivocal genotyping in 25 cases (approximately
89%). The remaining 3 cases were genotyped by dinucleotide
repeat marker (D13S133).
Conclusion: Sets of SNP markers are highly heterozygous
across most world populations and could be used
in combination with analysis of prevalent mutations as
a comprehensive strategy for determining presymptomatic
and carrier sibs of WD patients.
© 2007 American Association for Clinical Chemistry
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| Date |
2007
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/263/1/CLINICAL_CHEMISTRY%2C__53_(_9)%2C1601%2D1608%2C2008_[40].pdf
Gupta, Arnab and Maulik, Mahua and Nasipuri, Poonam and Chattopadhyay, Ishita and Das, Shyamal K and Gangopadhyay, Prasanta K and Ray, Kunal (2007) Molecular Diagnosis of Wilson Disease Using Prevalent Mutations and Informative Single- Nucleotide Polymorphism Markers. Clinical Chemistry, 53 (9). pp. 1601-1608. |
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| Relation |
http://dx.doi.org/10.1373/clinchem.2007.086066
http://www.eprints.iicb.res.in/263/ |
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