Polymerase chain reaction amplification of two polymorphic simple repeat sequences within the von Willebrand factor gene: application to family studies in von Willebrand disease

Abstract

We have used the polymerase chain reaction to amplify two variable number of tandem repeats (VNTRs) within a region of repetitive DNA located in intron 40 of the von Willebrand factor (vWf) gene. Heterozygosity for VNTR I was observed in 30 out of 39 normal unrelated individuals tested (77%), and for VNTR II in 29 out of 44 (66%) similar individuals. Family studies were carried out on 11 kindreds with von Willebrand disease (vWD). Ten of these families were found to be informative for one or other of the VNTRs or for a combination of data from both VNTRs. This method can be used for antenatal diagnosis and for carrier diagnosis in recessive forms of vWD. It is also useful for tracking the gene associated with vWD in type I families where there may be one or more individuals with a phenotypically uncertain diagnosis.

Instability in the ATCT variable number tandem repeat locus VWF.VNTR I in intron 40 of the von Willebrand factor gene

“…The ATCT variable number of tandem repeat (VNTR) locus, VWF.VNTR I located in intron 40 of the VWF gene has been found to be a useful genetic marker for parentage testing, forensic and diagnostic purposes Cumming et al, 1992;Gaucher et al, 1992;Haddad & Sparrow, 1997). This locus exhibits 10 alleles; the smallest has six ATCT motif repeats and is 103 base pairs in length, whilst the largest has 15 repeats and is 139 base pairs in length.…”

Two novel alleles of the ATCT variable number tandem repeat locus VWF.VNTR I in intron 40 of the von Willebrand factor gene

“…The VWF.VNTR I locus has been used for the determination of chimaerism following bone marrow transplantation (Gaiger et al, 1991) and for von Willebrand disease marker studies Cumming et al, 1992;Gaucher et al, 1992). The additional alleles (alleles 9 and 15) described here further enhance the usefulness of this VNTR locus, particularly for the purposes of paternity and forensic investigations.…”

An unexpected transmission of von Willebrand disease type 3: the first case of maternal uniparental disomy 12

“…For the segregation study, PCR amplifications of 16 polymorphic markers on chromosome 12 were carried out with fluorescent primers. Six were on the VWF gene, [6][7][8][9][10] and the other 10 were located on the short and the long arms of chromosome 12 and were selected on the GeneLoc database (http://genecards.weizmann.ac.il/geneloc/index.shtml). The amplification products were resolved on the ABI3130XL sequencer and ana- lyzed with GeneScanv3.7 (Applied Biosystems).…”