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E Bakker

Publications and source records attributed to E Bakker.

At least 181 records · Page 10Linked to original sources
PubMed1988

First trimester prenatal diagnosis of haemophilia A: two years' experience.

We evaluated the feasibility, reliability, and acceptability of prenatal diagnosis of haemophilia A by DNA analysis of chorionic villi. Twenty-two women at risk to transmit the abnormal gene were referred for prenatal diagnosis, two of them twice. Two of the 22 women appeared to be non-carriers by DNA analysis. In one of these women, the results were known only after chorionic villus sampling had been carried out. Thirteen of the twenty carriers were heterozygous for an intragenic (Bc1I or XbaI) marker; six women were only heterozygous for the extragenic DXS52 (St14) locus. One of the women was homozygous for all the presently known DNA markers within or closely linked with the factor VIII locus. Twelve of the 22 fetuses at risk were male, ten were female. Seven of the 12 male fetuses were shown to be affected and were subsequently aborted. Four male fetuses appeared to be not affected. In one case, the diagnosis was made by use of an extragenic marker. The woman rejected fetal blood sampling to confirm the diagnosis. After birth, a normal factor VIII level was found in three of the four cases. The fourth pregnancy is still continuing. In one of the 12 male fetuses, no diagnosis at the gene level was possible. DNA analysis is expected to provide maximum certainty as to the phenotype of the fetus for approximately 60 per cent of the women; for another 37 per cent a rate of misdiagnosis of 4-5 per cent applies. In only 3 per cent of the cases will no diagnosis at the gene level be possible as yet. The new possibility of a prenatal diagnosis in the first trimester of pregnancy enabled some of these women to have a family of their own and was appreciated in particular by the women who underwent fetoscopy in an earlier pregnancy.

DNA↗
PubMed1988

A deletion hot spot in the Duchenne muscular dystrophy gene.

We have made a detailed study of a deletion hot spot in the distal half of the Duchenne muscular dystrophy (DMD) gene, using intragenic probe P20 (DXS269), isolated by a hybrid cell-mediated cloning procedure. P20 detects 16% deletions in patients suffering from either DMD or Becker muscular dystrophy (BMD), in sharp contrast to the adjacent intragenic markers JBir (7%) and J66 (less than 1%), mapping respectively 200-320 kb proximal and 380-500 kb distal to P20. Of the P20 deletions, 30% start within a region of 25-40 kb, the majority extending distally. P20 was confirmed to map internal to a distal intron of the DMD gene. This region was recently shown by both cDNA analysis (M. Koenig et al., 1987; Cell 50: 509-517), and field inversion electrophoresis studies (J.T. Den Dunnen et al., 1987, Nature (London) 329: 640-642) to be specifically prone to deletions. In addition, P20 detects MspI and EcoRV RFLPs, informative in 48% of the carrier females. Together, these properties make P20 useful for carrier detection, prenatal diagnosis, and the study of deletion induction in both DMD and BMD.

Cell Line↗
PubMed1988

The anonymous RFLP locus D1S2 is close to PGM1 on chromosome 1.

D1S2 was one of the first restriction fragment length polymorphisms (RFLPs) assigned to chromosome 1, but its regional location was unknown. In this paper we present data that place this RFLP into both the genetic map and the physical-cytogenetic map. Linkage data maps D1S2 7 cM from PGM1, which is localized to the middle of the short arm at 1p22.1. Southern blot analysis of DNA samples from somatic cell hybrids containing parts of chromosome 1 maps D1S2 proximal to 1p32 and distal to PGM1.

Chromosomes, Human, Pair 1↗
PubMed1988

Duchenne muscular dystrophy: high frequency of deletions.

DNA probes are available for Duchenne muscular dystrophy (DMD) carrier detection and prenatal diagnosis. With probes for about 25% of the proximal portion of the gene, we found the proximal probes detected deletions in 23% of nonselected DMD boys, while a single distal probe detected 17% more as deletions. The combined percentage was 39% for all probes tested. Prenatal diagnosis and carrier detection are more accurate if deletions are mapped rather than by use of restriction fragment length polymorphism analysis. The effort involved in screening all affected boys for deletions is considerably less, and provides an accurate genetic marker for subsequent prenatal diagnosis in the family and prospective counseling for female relatives. It seems likely that, once the entire gene (cDNA) is available for screening, most DMD boys will show deletions.

Child↗
PubMed1987

Two genes homologous with human protein S cDNA are located on chromosome 3.

A cDNA coding for the carboxy-terminal region of human protein S and containing a complete 3'-untranslated region, was isolated by a combination of antibody screening of a lambda gt11 human liver cDNA expression library and in situ hybridization of a pUC9 human liver cDNA library. Hybridization analysis of human total DNA with radiolabelled non-overlapping cDNA restriction fragments revealed the existence of two genes per haploid genome homologous with the protein S cDNA. Both genes were mapped to chromosome 3 using human-rodent cell hybrids. Neither of the genes showed polymorphism for sixteen different enzymes upon hybridization with the protein S cDNA.

Chromosome Mapping↗
PubMed1987

Genotype assignment of haemophilia A by use of intragenic and extragenic restriction fragment length polymorphisms.

We performed DNA analysis in 20 families with haemophilia A in order to evaluate its usefulness for carrier detection and prenatal diagnosis. The polymorphic BclI site within intron 18 of the factor VIII gene and the extragenic TaqI and BglII polymorphic sites which are detected by the random DNA probes designated St14 and DX13, respectively, were investigated for. Two events of recombination were found between the St14 and the haemophilia A locus in 51 informative meioses. In one of these recombinant meioses crossing over had also occurred between the DX13 and the haemophilia A locus. No further crossovers between the DX13 and the haemophilia A locus were found in 20 informative meioses. Segregation analysis of the polymorphic markers and the deleterious mutation within the families allowed a diagnosis at the gene level for 52 out of 57 potential carriers. The new method considerably decreased the uncertainty about carriership for seventeen of the nineteen women with a probability of carriership between 5% and 95% based on pedigree analysis and factor VIII assays. In seven cases chromosome and DNA analysis of a chorionic villus biopsy was carried out. Three of the fetuses were female, four were male. Three of the male fetuses had inherited the normal maternal X-chromosome and were, therefore, not affected. For another male fetus no diagnosis at the gene level was possible since the mother was homozygous for all the known restriction fragment length polymorphisms within or closely linked with the haemophilia A locus.

Carrier State↗
PubMed1987

Long-range genomic map of the Duchenne muscular dystrophy (DMD) gene: isolation and use of J66 (DXS268), a distal intragenic marker.

By cloning the endpoints of a DMD-associated deletion, we have "jumped" 1100 kb from pERT87-1 (DSX164) to a new locus designated J66 (DXS268), mapping distally within the Duchenne muscular dystrophy (DMD) gene. Both J66 and JBir are mapped by field-inversion gel electrophoresis and detect abnormal SfiI fragments in DMD patients and distal DMD-associated X; autosome translocations. Our long-range map extends the physical map of the DMD gene from 800 to 2000 kb (2 Mb) and increases the mapped portion of Xp21 to approximately 8 Mb. The position of the glycerol kinase gene and the adrenal hypoplasia locus are further confined to the region between J66 and the nearest distal probe L1-4. This region spans at least 1.5 Mb. The multiallelic J66 polymorphism has immediate application in the diagnosis of DMD and generally appears to be distal to DMD mutations.

Chromosome Deletion↗
PubMed1987

The fragile X syndrome in a large family. III. Investigations on linkage of flanking DNA markers with the fragile site Xq27.

In a large family with the fragile X syndrome, we performed linkage investigations with six probes, detecting RFLPs at both sides of the fragile site Xq27. The nearest flanking markers were cX55.7 (DXS105) on the centromeric side (theta = 0.04, lod 5.0) and St14 (DXS52) on the telomeric side (theta = 0.08, lod 4.0). Non-penetrance could be shown by the presence of the grandpaternal X chromosome in three mentally retarded fra(X) positive males. A second non-penetrant male in this family had inherited an abnormal grandmaternal X chromosome. His carrier mother had two retarded fra(X) positive brothers. Intermediate between the non-penetrant and fully penetrant males was a non-retarded male, who expressed the fragile site in 6% of his cells. His X chromosome showed the same polymorphisms as were found in his seven severely retarded brothers. In five fra(X) negative females the presence of an abnormal X chromosome could be demonstrated. Despite the existence of non-penetrance in this pedigree, there was no close linkage between a factor IX polymorphism and the fragile site (theta = 0.16, lod 1.9). However, in six descendants of a non-penetrant male, the change to penetrance appeared to be accompanied by a low recombination frequency for flanking markers.

Factor IX↗
PubMed1987

Efficient isolation of X chromosome-specific single-copy probes from a cosmid library of a human X/hamster hybrid-cell line: mapping of new probes close to the locus for X-linked mental retardation.

We isolated X-chromosomal DNA probes from a cosmid library constructed from a single human X/hamster hybrid-cell line (C12D). One hundred human clones were isolated and used to construct a pool of X-chromosomal DNA. This DNA was digested into 0.15-2-kb fragments and subcloned into plasmids allowing the rapid characterization of new single-copy probes. These were regionally mapped and used for the detection of restriction-site polymorphisms. Together with a series of subcloned probes from individually isolated cosmids, we found seven polymorphic probes among 53 tested. Thirty-one of the probes were physically localized to different regions of the X chromosome. Four polymorphic probes map to Xq27-Xq28: DXS102 (cX38.1), DXS105(cX55.7), DXS107(cpX234), and DXS134(cpX67). These were genetically mapped by multipoint analysis relative to previously characterized loci, a mapping that resulted in the following order: DXYS1, DXS107, DXS51/DXS102, F9, DXS105, Fra-X, F8/DXS52, DXS15, DXS134. The mapping of DXS105 between F9 and Fra-X makes this probe useful for Fra-X analysis. For the linkage between FraX and DXS105, a maximum lod score of 5.01 at 4 cMorgans has been obtained in one large Dutch pedigree.

Animals↗
PubMed1986

A physical map of 4 million bp around the Duchenne muscular dystrophy gene on the human X-chromosome.

Employing pulsed field gradient electrophoresis, we constructed a 4.5 million bp (Mb) Sfil restriction map of the human X-chromosomal region p21, harboring genes for Duchenne (DMD) and Becker Muscular Dystrophy. In a DMD patient with additional chronic granulomatosis and retinitis pigmentosa, the proximal 3.5 Mb is deleted. Another DMD patient, with additional glycerol kinase deficiency and adrenal hypoplasia, lacks at least 3.3 Mb in the middle region, including marker C7 but not B24, placing C7 closer to DMD. Another DMD patient has a partial pERT-87 deletion of minimally 140 kb. Truncated Sfil fragments in a female X:21 translocation patient place the junction probe XJ1.1 115 kb from the distal end of the normal fragment. Probe pERT-84 maps to the same fragment, within 750 kb of XJ1.1.

Chromosome Aberrations↗
PubMed1986

Fine mapping of the Huntington disease linked D4S10 locus by non-radioactive in situ hybridization.

The chromosomal localization of a unique DNA fragment, closely linked to Huntington disease (HD), was assessed in situ by hybridization with 2-acetylaminofluorene (AAF) modified probes. In these experiments, a cosmid cloned genomic fragment (c5.5) was used for hybridization. Here we present evidence that confirms the mapping of the D4S10 locus to the p16 region of chromosome 4 and assigns it to the telomere of the short arm.

Chromosome Mapping↗
PubMed1986

Development of additional RFLP probes near the locus for Duchenne muscular dystrophy by cosmid cloning of the DXS84 (754) locus.

We have isolated 70kb of sequences surrounding probe 754 (DXS84), linked with Duchenne muscular dystrophy. In addition to the original PstI RFLP detected by 754, BglII and EcoRI RFLPs were detected with the single copy subclone 754.11 and a HindIII RFLP with the subclone 754.6. The BglII and HindIII and HindIII RFLPs both have minor allele frequencies of 40%, as in PstI polymorphism. The EcoRI polymorphism has a minor allele frequency of 23%. Since a linkage disequilbrium is observed between these RFLPs (P less than 0.001), the BglII and the HindIII RFLPs do not contribute to the heterozygosity. However, the minor allele of the EcoRI RFLP segregates exclusively with the major haplotype of the PstI-BglII-HindIII complex, and consequently 47% of the homozygotes for the haplotype become heterozygous. As a result, the overall heterozygote frequency of the DXS84 locus increases from 50% to 65%.

Chromosome Mapping↗