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O Riess

Publications and source records attributed to O Riess.

119 records · Page 7Linked to original sources
PubMed1991

The codon 408 mutation associated with haplotype 2 is predominant in Polish families with phenylketonuria.

The incidence of phenylketonuria (PKU) in the western part of Poland is 1 in 5000 live births. Restriction fragment length polymorphism (RFLP) haplotypes at the phenylalanine hydroxylase locus have been analysed in 46 Polish families with PKU. Among 43 fully-informative families 16 RFLP haplotypes were identified. Haplotype 2 is the most frequently (62%) associated with Polish PKU alleles, and the codon 408 mutation is in complete linkage disequilibrium with this haplotype in Poland. This finding is in agreement with observations in other eastern European countries (German Democratic Republic, Czechoslovakia, and Hungary) and in contrast to the genotype distribution observed in western European countries. The present observation suggests the spread of classical PKU, due to the codon 408 mutation associated with haplotype 2, from east to west in European populations. Perhaps more important for genetic counselling, 62% of all PKU chromosomes in the Polish population can now be detected using only one mutant-specific oligonucleotide probe.

Alleles↗
PubMed1991

Identification of multiple CpG islands and associated conserved sequences in a candidate region for the Huntington disease gene.

The HD locus has been assigned to 4p16.3 distal to the DNA segment D4S10. However, the precise location of this gene is still unknown. At least three regions, together encompassing more than 3.5 Mb of DNA, can still be considered as candidate regions for the HD gene. Our efforts are directed toward the cloning and the complete characterization of one of these regions. Thus far we have cloned 460 kb of DNA in contiguously overlapping cosmids distal to D4S111 and have developed a detailed long-range restriction map orienting the contig within the terminal region of 4p16.3. We characterized 15 CpG-rich islands defined by tightly clustered rare cutter restriction sites for the enzymes NotI, BssHII, EagI, NruI, and SacII. In addition, we show that the sequences associated with the CpG-rich islands detect cross-species conservation. The detailed genetic analysis of the 460-kb contig provides a framework for the identification of genes, which can be assessed for the characteristics expected for the HD gene.

Animals↗
PubMed1990

Hypervariability of intronic simple (gt)n(ga)m repeats in HLA-DRB genes.

We have investigated the extent of DNA variability in intronic simple (gt)n(ga)m repeat sequences and correlated this to sequence polymorphisms in the flanking exon 2 of HLA-DRB genes. The polymerase chain reaction (PCR) was used to amplify a DNA fragment containing exon 2 and the repeat region of intron 2. The PCR products were separated on sequencing gels in order to demonstrate length hypervariability of the (gt)n(ga)m repeats. In a parallel experiment, the PCR products were cloned and sequenced (each exon 2 plus adjacent simple repeats) to characterize the simple repeats in relation to the HLA-DRB sequences. In a panel of 25 DRB1, DRB4, and DRB5 alleles new sequences were not detected. Restriction fragment length polymorphism (RFLP) subtyping of serologically defined haplotypes corresponds to translated DNA sequences in 85% of the cases, the exceptions involving unusual DR/DQ combinations. Many identical DRB1 alleles can be distinguished on the basis of their adjacent simple repeats. We found group-specific organization of the repeats: the DRw52 supergroup repeats differ from those of DRB1*0101, DRB4*0101, and DRB5*0101 alleles and from those of pseudogenes. Finally, we amplified baboon DNA and found a DRB allele with extensive similarity to DRB1 sequences of the DRw52 supergroup. The simple repeat of the baboon gene, however, resembles that of human pseudogenes. In addition to further subtyping, the parallel study of polymorphic protein and hypervariable DNA alleles may allow conclusions to be drawn on the relationships between the DRB genes and perhaps also on the theory of trans-species evolution.

Amino Acid Sequence↗
PubMed1989

RFLP-discordance within the human phenylalanine hydroxylase locus.

A search for crossover events was performed in seven families with two phenylketonuria-affected children applying seven enzymes for the detection of eight restriction fragment length polymorphisms (RFLPs) by hybridisation with a human phenylalanine hydroxylase (PAH) cDNA probe. A discordance was detected within the PvuIIb-RFLP pattern of two affected sibs. This observation is most likely the result of a cross-over event in the PAH locus. Alternative explanations are discussed. Non-paternity could be excluded by DNA fingerprinting using the oligonucleotide probe (GTG)5.

Crossing Over, Genetic↗
PubMed1989

Haplotype analysis of the phenylalanine hydroxylase gene in Turkish phenylketonuria families.

We have estimated the haplotype distribution of mutant and normal phenylalanine hydroxylase (PAH) alleles for 17 Turkish phenylketonuria (PKU) families: 20 normal and 27 mutated PAH alleles could be identified. Of the latter, the most prevalent were associated with haplotype 6 (29.6%), 1 (18.5%) and 36 (11.1%), while the normal alleles were preferentially associated with haplotype 1 (20%). Of the 19 different haplotypes observed, 5 have not been described previously. The haplotype distribution differed significantly from that of the Northern European population. Two of the eight polymorphic sites were in association with PKU. No deletions of exon sequences were found in the families analysed.

Alleles↗
PubMed1988

Linkage disequilibrium between RFLP haplotype 2 and the affected PAH allele in PKU families from the Berlin area of the German Democratic Republic.

Probands from 26 PKU-affected families of the Berlin area were analyzed with respect to the allele frequency distribution of six RFLPs in linkage with the normal and the PKU alleles of the phenylalanine hydroxylase gene. These investigations confirm most of the RFLP haplotypes observed by Güttler and colleagues in the Danish population and describe two additional ones. They detect no significant differences in the single RFLP or RFLP haplotype distribution on the normal chromosomes in comparison with the Danish families and confirm a prevalent association of the RFLP haplotypes 1, 4, and 7 with the normal PAH allele. In contrast to the Danish investigations, in our study the PKU allele is found most frequently linked to haplotype 2, rather then to haplotype 3. In one of our patients we found a substitution of the normal 19-kb MspI fragment by a 13.5- and a 5.5-kb fragment, reported up to now only in one other German family.

Alleles↗
PubMed1987

Introduction of genomic diagnosis of classical phenylketonuria to the health care system of the German Democratic Republic.

The phenylketonuria (PKU) dispensary of the Children's Hospital of the Charité, Berlin, GDR, cares for about 140 affected families, representing about one-third of all PKU families in the GDR. Of these families, 15 expressed their desire for an additional child given the availability of a reasonably reliable prenatal diagnosis procedure. They were investigated by linked RFLP analysis applying a phenylalanine-hydroxylase-cDNA probe. Full genetic predictability for prospective fetuses could be obtained for all of them. In eight cases this was possible by the use of one restriction enzyme, and in the remaining seven by a combination of the information from two restriction-enzyme patterns. No recombination between linked RFLP and the PKU phenotype could be observed in 40 meioses from the investigation of eight families with two affected children each.

Delivery of Health Care↗
PubMed1986

Typing of families with classical phenylketonuria using three alleles of the Hindiii linked restriction fragment polymorphism, detectable with a phenylalanine hydroxylase cDNA probe. Family typing for PKU by linked HindIII RFLP.

A human phenylalanine hydroxylase cDNA clone was isolated from a human liver cDNA library. The size of the cDNA insert is approximately 2.4 kb and appears to be a near full length copy of a phenylalanine hydroxylase mRNA. This cDNA was used to probe for HindIII restriction enzyme polymorphisms in heterozygote typing of families with phenylketonuria. The use of three alleles of this polymorphism, as opposed to the two alleles as previously described, increases the informativity for typing - and therefore also for prenatal diagnosis - in certain families from 75% to 100%.

Alleles↗
PubMedDate not supplied

Hybridization and polymerase chain reaction amplification of simple repeated DNA sequences for the analysis of forensic stains.

We have evaluated oligonucleotide hybridization and amplification techniques with regard to quantity and quality of genomic DNA that is under investigation in practical forensic case work. In order to obtain sufficient information from analyzing stain material, we use hypervariable simple repeat sequences for individualization, which occur in all eukaryotic genomes. For the analysis of larger amounts of stains (greater than 500 ng DNA) the multilocus probes (CAC)5/(GTG)5* are superior because of their discrimination potential--provided that the hybridizing DNA is of high molecular weight. The less discriminating probes (CT)8 and (GACA)4 are more sensitive (minimal amount: 100ng DNA) and still informative when the DNA is degraded. To increase the sensitivity of forensic stain analysis in special cases we have used the polymerase chain reaction technique to amplify hypervariable simple (gt)n/(ga)m repeat structures from the intron 2 of HLA-DRB genes. Largely independent of the starting amount of DNA and independent of the degradation status, we were able to generate discriminating DNA fragments, which can be used to type (i) microstains and (ii) totally degraded material including human mummy DNA.

Base Sequence↗
PubMedDate not supplied

Prenatal diagnosis of classical phenylketonuria by linked restriction fragment length polymorphism analysis.

Since the isolation of a recombinant containing a cDNA sequence for human phenylalanine hydroxylase (hPH) (Woo et al., 1983; Speer et al., 1986) prenatal diagnosis by linked restriction fragment length polymorphism (RFLPs) has become possible for families in which phenylketonuria (PKU) occurs (Lidsky et al., 1985a). We describe here the application of a Hind III three-allele RFLP in a single family, which allowed the prenatal diagnosis of an affected fetus.

Autoradiography↗