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H Scheffer

Publications and source records attributed to H Scheffer.

86 records · Page 5Linked to original sources
PubMed1990

Close linkage of the Wilson's disease locus to D13S12 in the chromosomal region 13q21 and not to ESD in 13q14.

Wilson's disease (WD) is an autosomal recessive disorder resulting in copper accumulation notably in liver and brain tissue. Linkage of the WD locus (WND) to ESD at 13q14 was first shown by studies in families of Middle Eastern origin using the isozymic polymorphism of esterase D. Using RFLPs detected by the ESD cDNA we could not confirm this reported close linkage in an analysis of 17 WD families of northwest European origin. A tight linkage was detected, however, to the marker D13S12, located more distally at 13q21. No obligate cross-overs were detected in 63 gametes informative for this marker. Our data confirm an assignment of WND to 13q14-21. Its localization, however, seems to be more distal to ESD than previously reported. Although genetic heterogeneity cannot be excluded, the observed differences between the two populations are probably due to random variation.

Carboxylesterase↗
PubMed1990

Frequency of the delta F508 mutation and XV2c,KM19 haplotypes in cystic fibrosis families from The Netherlands: haplotypes without delta F508 still in disequilibrium.

We have determined the frequency of the major cystic fibrosis (CF) three base pair deletion (delta F508) mutation in 152 CF chromosomes from patients originating from the northern part of The Netherlands. In these patients, the deletion represents approximately 76% of CF mutations. Meconium ileus is strongly associated with homozygosity for the delta F508 mutation. The XV2c,KM19 haplotypes on the CF chromosomes without the delta F508 mutation are in disequilibrium with the population frequency, although showing an increased frequency of the 1 2 haplotype. The surplus of this haplotype is almost entirely made up by the pancreatic insufficient patients.

Cystic Fibrosis↗
PubMed1989

Linkage analysis of families with hereditary retinoblastoma: nonpenetrance of mutation, revealed by combined use of markers within and flanking the RB1 gene.

Nonpenetrance of the inherited mutation responsible for retinoblastoma has been reported. By DNA analysis in families with hereditary retinoblastoma, it is possible to identify healthy individuals in whom the mutation is nonpenetrant. This requires the use of DNA markers both within and flanking the retinoblastoma gene. We have analyzed the segregation of several markers in 19 families (69 meioses) with hereditary retinoblastoma. In two families a carrier was identified who showed nonpenetrance of the mutation predisposing to retinoblastoma. The intragenic markers were informative in 15 pedigrees. The use of flanking markers from the same chromosomal region caused an increase of the number of informative families to 18. No crossing-over within the gene was observed. In one family an inherited deletion involving one of the RB1 alleles was detected. Our findings emphasize the use of a combination of both intragenic and flanking markers to obtain both the highest reliability of carrier detection in families with hereditary retinoblastoma and an accurate estimate of the frequency of nonpenetrance.

Chromosome Deletion↗
PubMed1988

A human glioblastoma line with karyotypic nullisomy 13 containing several chromosome 13-specific sequences.

Using a biochemical approach (evaluation of esterase D activity) and recombinant DNA techniques (in situ and filter hybridization with specific DNA probes) a glioblastoma cell line with karyotypical nullisomy 13 was shown to contain several chromosome #13-specific sequences. They were assigned to a marker chromosome. This finding suggests that cytogenetic descriptions of deletions or chromosome losses will gain considerable power of the statement when supplemented by molecular analysis, particularly since, by now, DNA probes have been accumulated for all chromosomes and all their subfragments.

Chromosome Banding↗
PubMed1988

Eight closely linked loci place the Wilson disease locus within 13q14-q21.

Wilson disease (WD) is an autosomal recessive disorder resulting in an accumulation of copper in the liver, brain, and other organs. The WD locus (WND) has previously been linked to esterase D (ESD) and localized to 13q14-22. With the large Centre d'Etude Polymorphisme Humain cohort, a refined map of DNA markers from this region was constructed, with the following locus order: D13S1-D13S21-D13S22-D13S10-ESD-RB-WND-D 13S26-D13S12-D13S2. A significant excess of male recombination was observed between D13S21 and D13S22. Intervals distal to D13S22 showed an excess of female recombination. When these markers were tested on 19 WD families from a variety of ethnic backgrounds, the two closest loci were shown to be RB and D13S26. The retinoblastoma gene locus (RB) was shown to be proximal to WND at a distance of 4.4 centimorgans (cM), and D13S26 was placed distal to WND at a distance of 4.0 cM. ESD was assigned proximally at a distance of 9.4 cM. In all families studied WND was linked to one or more of the loci ESD, RB, or D13S26.

Chromosome Mapping↗
PubMed1987

Localization at a subband level of polymorphic 13q14 DNA probes for diagnosis of hereditary retinoblastoma and Wilson disease.

Two single-copy DNA sequences, pG24E6.8 (D13S21) detecting a low-frequency MspI RFLP and pG14E1.9 (D13S22) detecting a high-frequency Dra I RFLP, have been isolated and cloned from a human chromosome 13-specific phage library and localized at 13q14. Their subband localization was described using a panel of cell lines from patients with different chromosome 13 deletions. A quantitative analysis of hybridization signals was carried out, taking for reference a single-copy DNA sequence from another chromosome. D13S21 and D13S22 were both assigned to q14.1-14.2, which also harbors the genes responsible for retinoblastoma and Wilson disease. The Dra I polymorphism detected by pG14E1.9 is a very suitable one for linkage studies in families with either disease.

Cell Line↗
PubMed1986

A straightforward approach to isolate DNA sequences with potential linkage to the retinoblastoma locus.

From a human-Chinese hamster somatic cell hybrid a clone was derived containing chromosome 13 in duplicate as its only human material. This clone was used to construct a human chromosome 13-specific recombinant DNA-library. Overlapping Sau3AI DNA sequences (11.9-17.2 kb) from the cell hybrid were inserted into the lambda phage vector EMBL4. From eleven recombinants having a human insert thirteen putative unique DNA sequences were isolated and cloned into the plasmid vector pBR329. A human-mouse hybrid containing a human chromosome 13 with a deletion of 13q14 and lacking its undeleted homologue was constructed to be used in a selection procedure for DNA sequences belonging to band q14. Three probes originating from two different phages were assigned to 13q14 because they did not hybridise to DNA from this cell hybrid. One of these 13q14 probes detects a low frequency (2/44) MspI restriction fragment length polymorphism. The probes are now being used for screening a cosmid library to find adjacent polymorphic sequences with a RFLP information content suitable for application in the diagnosis of hereditary retinoblastoma.

Animals↗