Numerous polymorphic microsatellites in the human prion gene complex (including PRNP, PRND and PRNT)

Preuß, Siegfried; Peischl, T.; Melchinger, Elke; Geldermann, H.

doi:10.1016/j.gene.2003.12.030

Cited by 5 publications

(6 citation statements)

References 12 publications

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“…The differences found in the number of alleles and the heterozygosity rate are probably attributable to the higher number of control individuals analysed, viz. 50 in the present study versus 18 in the study of Preuss et al (2004). Therefore, our data indicate that marker MsP6 is highly informative and is of great interest for haplotype analyses in the context of founder effects studies of the PRNP D178N mutation.…”

Section: Discussionmentioning

confidence: 50%

“…Three of them (MsP2, MsP4, MsP6) have been recently described by Preuss et al (2004); markers MsP2 and MsP4, which correspond to their M03 and M11, respectively, show similar heterozygosity values, whereas marker MsP6 corresponds to M12 and shows higher values of heterozygosity than the 0.56 given by Preuss et al (2004). Furthermore, for this marker, they observed alleles with 18 to 22 repetitions, whereas alleles of 16, 17 and 23 repetitions were found in the population sample from the Basque Country and the Aquitaine Region.…”

Section: Discussionmentioning

confidence: 99%

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Ancestral origins of the prion protein gene D178N mutation in the Basque Country

Rodríguez-Martínez

Barreau

Coupry³

et al. 2005

Hum Genet

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Fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD) are familial prion diseases with autosomal dominant inheritance of the D178N mutation. FFI has been reported in at least 27 pedigrees around the world. Twelve apparently unrelated FFI and fCJD pedigrees with the characteristic D178N mutation have been reported in the Prion Diseases Registry of the Basque Country since 1993. The high incidence of familial prion diseases in this region may reflect a unique ancestral origin of the chromosome carrying this mutation. In order to investigate this putative founder effect, we developed "happy typing", a new approach to the happy mapping method, which consists of the physical isolation of large haploid genomic DNA fragments and their analysis by the Polymerase Chain Reaction in order to perform haplotypic analysis instead of pedigree analysis. Six novel microsatellite markers, located in a 150-kb genomic segment flanking the PRNP gene were characterized for typing haploid DNA fragments of 285 kb in size. A common haplotype was found in patients from the Basque region, strongly suggesting a founder effect. We propose that "happy typing" constitutes an efficient method for determining disease-associated haplotypes, since the analysis of a single affected individual per pedigree should provide sufficient evidence.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Ancestral origins of the prion protein gene D178N mutation in the Basque Country

Rodríguez-Martínez

Barreau

Coupry³

et al. 2005

Hum Genet

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“…A 20 μl PCR reaction mix contained 200 μM of each dNTP, 100 ng template DNA, 0.5 U Taq-Polymerase and 0.15 μM of each primer, one of them being Fluorescein labelled. The primer sequences of the microsatellite sites and OCTA were described by Preuss et al (2004). Denaturation at 94°C for 2 min was followed by 32 cycles with denaturation (94°C; 15 s), annealing (56-62°C; 45 s) and extension (72°C; 45 s).…”

Section: Microsatellites Pcr Conditions and Fragment Length Analysismentioning

confidence: 99%

“…We regarded microsatellites with at least four repeats and 90% of homology in our screening (Preuss et al, 2004) within 148 kb of the human PRNP segment (GenBank acc. no.…”

Section: Microsatellite Sitesmentioning

confidence: 99%

“…Thus, several sites along the prion gene complex may contain variable nucleotides that affect the CJD susceptibility. The aim of this study was to evaluate CJD associations of new polymorphic microsatellite sites that we detected in a previous study within 148 kb of the human prion gene complex, including the genes PRNP, PRND and PRNT (Preuss et al, 2004). Microsatellite sequences are often highly polymorphic and therefore informative for the analysis of gene effects.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphic microsatellite sites in the PRNP region point to excess of homozygotes in Creutzfeldt–Jakob disease patients

Geldermann

Bartenschlager

Preuß

et al. 2006

Gene

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Molecular evidence of founder effects of fatal familial insomnia through SNP haplotypes around the D178N mutation

et al. 2008

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This work presents a detailed investigation of the genomic region surrounding the PRNP gene in a sample of patients diagnosed with fatal familial insomnia (FFI) from several European countries, notably Spain. The main focus of the study was to explore the origins of the chromosomes carrying the D178N mutation by designing a single-nucleotide polymorphism (SNP) haplotype around the PRNP gene. Haplotypes were constructed by genotyping six SNPs (rs2756271, rs13040327, rs6037932, rs13045348, rs6116474, and rs6116475) in 25 FFI patients from all over Spain. To augment the geographical scope of our study, 13 further FFI cases from Germany (9) and Italy (4) were also examined. Genotyping of SNPs in conjunction with the analysis of genealogical data for a group of FFI patients revealed the existence of two distinct haplotypes potentially associated with the D178N mutation. Of them, GCATTA-M proved to be the common haplotype of Spanish patients, whereas ACATTA-M was typical of the German cases. It is interesting to note that both haplotypes were identified in the Italian samples: GCATTA-M in a family from the Tuscany region and ACATTA-M in a family from the Veneto region. Our findings suggest the occurrence of two independent D178N-129M mutational events in Europe, preserved and transmitted from one generation to the next until nowadays. Likewise, results based on the analysis of SNP data indicate that previous hypotheses postulating that the D178N mutation had independent origins for each family and that its global distribution was determined by recurrent mutational events must be regarded with caution.

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Numerous polymorphic microsatellites in the human prion gene complex (including PRNP, PRND and PRNT)

Cited by 5 publications

References 12 publications

Ancestral origins of the prion protein gene D178N mutation in the Basque Country

Ancestral origins of the prion protein gene D178N mutation in the Basque Country

Polymorphic microsatellite sites in the PRNP region point to excess of homozygotes in Creutzfeldt–Jakob disease patients

Molecular evidence of founder effects of fatal familial insomnia through SNP haplotypes around the D178N mutation

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