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J L Mandel

Publications and source records attributed to J L Mandel.

At least 199 records · Page 11Linked to original sources
PubMed1986

Characterization of a set of X-linked sequences and of a panel of somatic cell hybrids useful for the regional mapping of the human X chromosome.

We have characterized 19 DNA fragments originating from the human X chromosome. Most of them have been isolated from an X chromosome genomic library (Davies et al. 1981) using a systematic screening procedure. These DNA probes have been used to search for restriction fragment length polymorphisms (RFLP). The frequency of restriction polymorphisms (1 per 350 bp analysed) was lower than expected from data obtained with autosomal fragments. The various probes have been mapped within 12 subchromosomal regions using a panel of human-rodent hybrid cell lines. The validity of the panel was established by hybridization experiments performed with 27 X-specific DNA probes, which yielded information on the relative position of translocation breakpoints on the X chromosome. The DNAs from the various hybrid lines are blotted onto a reusable support which allows one to quickly map any new X-specific DNA fragment. The probes already isolated should be of use to map unbalanced X chromosome aberrations or to characterize new somatic cell hybrid lines. The probes which detect RFLPs define new genetic markers which will help to construct a detailed linkage map of the human X chromosome, and might also serve for the diagnosis of carriers or prenatal diagnosis.

Animals↗
PubMed1986

A case of female hemophilia with a 46,XXr karyotype studied with X-chromosome DNA probes.

A case of female hemophilia with a 46,XXr/45,X karyotype and signs of Turner syndrome, has been followed for the past 10 years. One of her brothers also has hemophilia A. A study with polymorphic DNA probes located in the Xq27-qter region has enabled us to demonstrate that the ring chromosome is of paternal origin and that the factor VIII gene region is deleted. The hemizygous state allowed expression of the hemophilia A mutation, present on the morphologically normal X chromosome, inherited from her carrier mother.

Adolescent↗
PubMed1985

Homologies between X and Y chromosomes detected by DNA probes: localisation and evolution.

We have isolated and characterized DNA probes that detect homologies between the X and Y chromosomes. Clone St25 is derived from the q13-q22 region of the X chromosome and recognizes a 98% homologous sequence on the Y chromosome. Y specific fragments were present in DNAs from 5 Yq-individuals and from 4 out of 7 XX males analysed. An X linked TaqI RFLP is detected with the St25 probe (33% heterozygosity) which should allow one to establish a linkage map including other polymorphic X-Y homologous sequences in this region and to compare it to a Y chromosome deletion map. Probe DXS31 located in Xp223-pter detects a 80% homologous sequence in the Y chromosome. The latter can be assigned to Yq11-qter outside the region which contains the Y specific satellite sequences. ACT1 and ACT2, the actin sequences present on the X and Y chromosomes respectively, have been cloned. No homology was detected between the X and Y derived fragments outside from the actin sequence. ACT2 and the Y specific sequence corresponding to DXS31 segregate together in a panel of Y chromosomes aberrations, and might be useful markers for the region important for spermatogenesis in Yq. Various primate species were analysed for the presence of sequences homologous to the three probes. Sequences detected by St25 and DXS31 are found only on the X chromosome in cercopithecoidae. The sequences which flank ACT2 detect in the same species autosomal fragments but no male specific fragments. It is suggested that the Y chromosome acquired genetic material from the X chromosome and from autosomes at various times during primate evolution.

Actins↗
PubMed1985

Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs.

By the use of a series of closely linked DNA probes detecting restriction fragment length polymorphisms (RFLPs) distributed over the short arm of the X chromosome, a double crossover was detected in a Duchenne muscular dystrophy carrier and an affected male fetus was diagnosed at 12 weeks of gestation, with a probable accuracy of more than 99.0%. A new mutation was identified in another family with the same degree of reliability; three females in this family were thus deemed not to be DMD carriers. The eleven RFLP-markers presently available on the short arm of the X chromosome are useful in the diagnosis of DMD since they bridge the Duchenne locus at genetic distances varying between 3 and 20 cmo. Moreover, recombination within the set of markers provides an independent way of regionally mapping these probes relative to each other along the short arm of the X chromosome.

Chromosome Mapping↗
PubMed1985

Genetic screening for hemophilia A (classic hemophilia) with a polymorphic DNA probe.

We have developed a new method of screening for hemophilia A in families at risk for the disease. A DNA probe (St14) that detects a very polymorphic region on the human X chromosome has been shown to be closely linked to hemophilia A. We observed no recombination between the St14 locus and hemophilia A in 12 families studied. The odds in favor of linkage are 4.4 X 10(9) to 1 (lod score, 9.65). The 95 per cent confidence interval for the probability of a recombination between St14 and hemophilia A is 0 to 6.5 per cent. This DNA probe, which is informative in more than 90 per cent of families at risk of hemophilia A, can be used in conjunction with classic biologic assays to identify carriers with an accuracy of 96 per cent or more. If a small risk of misclassification due to crossover between the test and the disease loci is accepted, this DNA marker should allow first-trimester prenatal diagnosis of hemophilia A. Segregation analysis with St14 may thus represent a major improvement in genetic counseling for hemophilia A.

Alleles↗
PubMed1985

Extensive DNA sequence homologies between the human Y and the long arm of the X chromosome.

It has been proposed that sequence homology should exist between the short arms of the human sex chromosomes, in the regions pairing at meiosis. Out of 40 clones picked at random from a collection of non-repetitive DNA sequences derived from the human Y chromosome, we have found nine sequences which show very high homology with sequences located on the X chromosome. All nine probes originate from the euchromatic part of the Y chromosome. All the homologous sequences are located within the Xq12-Xq22-24 region. None of them map to the short arm of the X chromosome. We conclude that an important part of the euchromatic region of the Y chromosome is homologous to the middle of the X chromosome long arm, possibly as a result of recent translation event(s).

Animals↗
PubMed1985

Segregation analysis of a marker localised Xp21.2-Xp21.3 in Duchenne and Becker muscular dystrophy families.

A DNA marker C7, localised Xp21.1-Xp21.3, has been studied in kindreds segregating for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). In DMD families four crossovers were observed in 38 informative meioses between C7 and the DMD locus (theta = 0.12, z max = +2.72). In BMD families no recombinants were observed in the 16 informative meioses studied. These data are consistent with the localisation of the mutations in these disorders being in the same region of Xp21. Studies in families also segregating for the DNA marker 754 support the previously reported physical order of these loci as X centromere-754-DMD-BMD-C7-X telomere. A recombination fraction of 0.11 (z max = +5.58) was found between DMD-754 by combining our previously published data with the data presented here. C7 and 754 thus provide good bridging markers for the diagnosis of DMD and BMD.

Chromosome Banding↗
PubMed1985

Localization by in situ hybridization of the coagulation factor IX gene and of two polymorphic DNA probes with respect to the fragile X site.

The coagulation factor IX gene and two other polymorphic loci corresponding to DNA probes 52 A and St 14 have been previously localized in the q27 to qter region of the human X chromosome. In order to study their localization with respect to the fragile site at Xq27-28, we have hybridized the three DNA probes to metaphase chromosomes of a boy with fragile X mental retardation. We show that probe 52 A is located in the proximal part of the Xq27 band, while the coagulation factor IX gene is on the distal part of this band, but proximal to the fragile site. The very polymorphic St 14 probe is located in the distal part of the Xq28 band, on the other side of the fragile site.

Chromosome Banding↗
PubMed1985

First trimester prenatal diagnosis of adrenoleukodystrophy by determination of very long chain fatty acid levels and by linkage analysis to a DNA probe.

A first trimester prenatal diagnosis of adrenoleukodystrophy has been done on chorionic villi biopsy in the pregnancy of a carrier woman. Two different approaches allowed one to determine that the male fetus was affected: the linkage analysis of DNA from chorionic villi using the highly polymorphic probe St 14 and the determination of very long chain fatty acid levels in cultured chorionic villi.

Adrenoleukodystrophy↗
PubMed1985

A new MspI restriction fragment length polymorphism in the hemophilia B locus.

Using a partial cDNA probe for human coagulation factor IX, we have detected a new restriction fragment length polymorphism in human DNA digested with MspI. The frequency of the minor allele is 0.20 +/- 0.05 and average heterozygosity is about 0.32. The MspI RFLP is in strong linkage disequilibrium with the TaqI RFLP previously described, but should nevertheless be useful in segregation analysis in case of homozygosity for the TaqI minor allele.

Alleles↗
PubMed1985

The telomeric region of the human X chromosome long arm: presence of a highly polymorphic DNA marker and analysis of recombination frequency.

A DNA fragment (named St14) derived from the human X chromosome reveals a small family of related sequences that have been mapped to the Xq26-Xq28 region by using a panel of rodent-human somatic cell hybrids. The probe detects in human DNA digested by Taq I a polymorphic system defined by a series of at least eight allelic fragments with a calculated heterozygosity in females of 80%. With Msp I, we found three additional restriction fragment length polymorphisms, each of them being defined by two alleles. These polymorphisms are also common in Caucasian populations. The genetic locus defined by probe St14 has been localized more precisely to the distal end of the X chromosome (in band q28) by linkage analysis to other polymorphic DNA markers. The results obtained suggest that the frequency of recombination is distributed very unevenly in the q27-qter region of the X chromosome, with a cluster of seven tightly linked loci in q28 showing about 30% recombination with the gene for coagulation factor IX located in the neighboring q27 band. Probe St14 reveals one of the most polymorphic loci known to date in the human genome, and 17 different genotypes have already been observed. It constitutes the best marker on the X chromosome and should be of great use for the genetic study of three important diseases: hemophilia A, mental retardation with a fragile X chromosome, and adrenoleukodystrophy.

Alleles↗