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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Thrombosis Research
Article . 2012 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
Thrombosis Research
Article . 2012
Data sources: u:cris
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Identification of an ancient haemophilia A splice site mutation

Authors: Reitter-Pfoertner, Sylvia; von Haeseler, Arndt; Horvath, Birgit; Sunder-Plassmann, Raute; Tiedje, Vera; Pabinger, Ingrid; Mannhalter, Christine;

Identification of an ancient haemophilia A splice site mutation

Abstract

To date, numerous mutations resulting in haemophilia A are known and recorded at HAMSTeRS. We identified a new splice site mutation in intron 6 of the F8 gene (T to G transition at position -14; c.788-14T>G) in seven not knowingly related patients, who all suffer from mild haemophilia A. RNA analysis of blood cells indicated that this mutation leads to the preferred generation of a transcript lacking the complete exon 7 (without frameshift).To determine whether the mutation represented a founder mutation we analyzed intragenic (intronic) and extragenic short tandem repeat (STR) regions and constructed haplotypes in the 7 patients and 128 apparently healthy male control individuals.In the 128 healthy control individuals, 109 different haplotypes were found. Surprisingly, also the 7 patients carried 3 different haplotypes. However, by genealogy reconstruction using BATWING we could identify an ancestral haplotype on which the mutation apparently occurred. This haplotype - DXS9897:12-DXS1073:21-HA472:64-DXS1108:26 - was frequent and was found in three patients, but was also present in four control individuals who did not carry the splice site mutation.Our data indicate that the splice site mutation occurred in an individual carrying a relatively common haplotype. While the mutation was passed on through generations, the haplotypes identified in the seven patients derived from this founder haplotype but were changed by later mutations in the STR regions.

Keywords

Male, Heterozygote, Factor VIII, Genetic Carrier Screening, 106023 Molecular biology, Middle Aged, Hemophilia A, Founder Effect, Introns, 106023 Molekularbiologie, Austria, Mutation, Humans, Female, Genetic Predisposition to Disease, RNA Splice Sites

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
7
Average
Average
Average