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J Overhauser

Publications and source records attributed to J Overhauser.

At least 73 records · Page 4Linked to original sources
PubMed1994

Molecular and phenotypic mapping of the short arm of chromosome 5: sublocalization of the critical region for the cri-du-chat syndrome.

Forty-nine individuals have been identified with deletions or translocations involving the short arm of chromosome 5. While most display the classical phenotype of the cri-du-chat syndrome, several of the patients do not have the syndrome or have only a subset of the clinical features. Somatic cell hybrids containing the deleted chromosome 5 were derived from each patient. Each somatic cell hybrid was analyzed at the DNA level using 136 chromosome 5p-specific DNA fragments. It was possible to unambiguously order most of the chromosomal breakpoints present in the somatic cell hybrids based on the hybridization patterns of Southern blots. Further comparisons between the deletions present in the patients and their clinical features identified several chromosomal regions that were involved in specific clinical features. A critical chromosomal region involved the high-pitched cry mapped to 5p15.3, while the chromosomal region involved in the remaining features of the cri-du-chat syndrome mapped to a small region within 5p15.2. Deletions that did not include these two chromosomal regions presented varying clinical phenotypes from severe mental retardation and microcephaly to a clinically normal phenotype. These results demonstrate the need for careful characterization of a 5p deletion in prenatal cases before clinical predictions are made.

Animals↗
PubMed1994

Molecular mapping of the Edwards syndrome phenotype to two noncontiguous regions on chromosome 18.

In an effort to identify regions on chromosome 18 that may be critical in the appearance of the Edwards syndrome phenotype, we have analyzed six patients with partial duplication of chromosome 18. Four of the patients have duplications involving the distal half of 18q (18q21.1-qter) and are very mildly affected. The remaining two patients have most of 18q (18q12.1-qter) duplicated, are severely affected, and have been diagnosed with Edwards syndrome. We have employed FISH, using DNA probes from a chromosome 18-specific library, for the precise determination of the duplicated material in each of these patients. The clinical features and the extent of the chromosomal duplication in these patients were compared with four previously reported partial trisomy 18 patients, to identify regions of chromosome 18 that may be responsible for certain clinical features of trisomy 18. The comparative analysis confirmed that there is no single region on 18q that is sufficient to produce the trisomy 18 phenotype and identified two regions on 18q that may work in conjunction to produce the Edwards syndrome phenotype. In addition, correlative analysis indicates that duplication of 18q12.3-q22.1 may be associated with more severe mental retardation in trisomy 18 individuals.

Abnormalities, Multiple↗
PubMed1994

Interstitial deletions are not the main mechanism leading to 18q deletions.

Most patients who present with the 18q- syndrome have an apparent terminal deletion of the long arm of chromosome 18. For precise phenotypic mapping of this syndrome, it is important to determine whether the deletions are terminal deletions or interstitial deletions. A human telomeric YAC clone has been identified that hybridizes specifically to the telomeric end of 18q. This clone was characterized and used to analyze seven patients with 18q deletions. By FISH and Southern blotting analysis, all patients were found to lack this chromosomal region on their deleted chromosome, demonstrating that the patients do not have cryptic interstitial deletions.

Base Sequence↗
PubMed1993

Genetic syndromes and uniparental disomy: a study of 16 cases of Brachmann-de Lange syndrome.

Uniparental disomy is responsible for a proportion of cases in Prader-Willi, Angelman, and Wiedemann-Beckwith syndromes. In these syndromes, the chromosomes involved are thought to contain one or more imprinted genes. When two copies of the imprinted (inactivated) gene are inherited from a single parent through uniparental disomy or the active gene is deleted, the phenotype of the syndrome results. Our goal is to identify additional syndromes caused by uniparental disomy. Our approach is to select syndromes that appear to have more than one mode of inheritance and are occasionally associated with a cytogenetic abnormality. Given this criterion, we have chosen Brachmann-de Lange Syndrome (BDLS) to investigate since the phenotype is similar to that found in patients with dup(3q). We have studied 16 probands with BDLS and their parents using a multiplex of four PCR-based polymorphic loci on chromosome 3. None of the probands studied had uniparental disomy for chromosome 3 and all demonstrated normal biparental inheritance for at least one locus. Given these results, uniparental disomy of chromosome 3 does not appear to be a major contributor to the syndrome. Additionally, both maternally and paternally derived chromosome abnormalities have resulted in the dup(3q) phenotype and dominant inheritance of BDLS from both mildly affected mothers and fathers have been reported which suggests that imprinting is not involved in these syndromes.

Chromosomes, Human, Pair 3↗
PubMed1993

A microsatellite genetic linkage map of human chromosome 18.

We isolated nine new microsatellite markers from chromosome 18 and further characterized and mapped eight microsatellites developed in other laboratories. We have constructed a framework linkage map of chromosome 18 that includes 14 microsatellite markers (12 dinucleotide and 2 tetranucleotide) and 2 RFLP markers. Cytogenetic localization for the microsatellites was performed by PCR amplification of 18 somatic cell hybrids containing different deletions of chromosome 18. Twelve of the microsatellites and one of the RFLPs have heterozygosites greater than 70%. The average heterozygosity of the markers included in the map is 72%. In addition, we have made provisional placements of 3 more microsatellite markers and 2 more RFLP markers. The map lengths (in Kosambi centimorgans) are as follows: sex-averaged, 109.3 cM; male, 72.4 cM; female, 161.2 cM. The average distance between markers in the sex-averaged map is 7.3 cM, and the largest gap between markers is 16.7 cM. Analysis of the data for differences in the female:male map distance ratio revealed significant evidence for a constant difference in the ratio (chi 2 = 32.25; df = 1; P < 0.001; ratio = 2.5:1). Furthermore, there was significant evidence in favor of a variable female:male map distance ratio across the chromosome compared to a constant distance ratio (chi 2 = 27.78; df = 14; P = 0.015). To facilitate their use in genomic screening for disease genes, all of the microsatellite markers used here can be amplified under standard PCR conditions, and most can be used in duplex PCR reactions.

Base Sequence↗
PubMed1993

STS map of genes and anonymous DNA fragments on human chromosome 18 using a panel of somatic cell hybrids.

Somatic cell hybrids containing different deleted regions of chromosome 18 derived from patients with balanced translocations or terminal deletions were used to create a deletion mapping panel. Twenty-four sequence-tagged sites (STSs) for 17 genes and 7 anonymous polymorphic DNA fragments were identified. These STSs were used to map the 24 loci to 18 defined regions of chromosome 18. Both ERV1, previously mapped to 18q22-q23, and YES1, previously mapped to 18q21.3, were found to map to 18q11.21-pter. Several genes previously mapped to 18q21 were found to be in the order cen-SSAV1-DCC-FECH-GRP-BCL2-PLANH2-tel. The precise mapping of genes to chromosome 18 should help in determining whether these genes may be involved in the etiology of specific chromosomal syndromes associated with chromosome 18. The mapping of the polymorphic loci will assist in the integration of the physical map with the recombination map of chromosome 18.

Base Sequence↗
PubMed1993

The leukemia inhibitory factor receptor (LIFR) gene is located within a cluster of cytokine receptor loci on mouse chromosome 15 and human chromosome 5p12-p13.

The leukemia inhibitory factor receptor (LIFR) gene was localized to human chromosome 5p12-p13 by somatic cell hybrid analysis. Interspecific backcross analysis revealed that the murine locus was on chromosome 15 in a region of homology with human chromosome 5p. In both human and mouse genomes, the LIFR locus was linked to the genes encoding the receptors for interleukin-7, prolactin, and growth hormone.

Animals↗
PubMed1993

The human cytochrome b5 gene and two of its pseudogenes are located on chromosomes 18q23, 14q31-32.1 and 20p11.2, respectively.

Using very high stringency hybridization conditions for the Southern blot hybridization analysis of hamster-human cell hybrid DNA, we were able to map the human cytochrome b5 gene and two of its pseudogenes (psgb(5)1 and psgb(5)2) unambiguously to chromosomes 18, 14, and 20. These localizations were confirmed and extended to 18q23, 14q31-32.1, and 20p11.2 by using a combination of nonisotopic in situ hybridization of chromosomal spreads and the polymerase chain reaction analysis of DNA samples isolated from somatic cell hybrids retaining deletions or translocations of chromosome 18.

Animals↗
PubMed1993

Confirmation of isochromosome 18p using whole chromosome arm-specific fluorescence in situ hybridization.

Fluorescent in situ hybridization (FISH) using a pool of DNA clones that have been mapped to the short arm of chromosome 18 is described. This arm-specific painting technique was used to analyze the chromosomes of two patients who displayed different clinical pictures. One patient had clinical features consistent with tetrasomy 18p, and the other patient had some of the clinical features associated with trisomy 18. The initial karyotype of both patients showed the presence of a small metacentric marker chromosome, thought to resemble an iso(18p). This interpretation of the karyotype was confirmed for both cases using a specific chromosome arm-painting strategy. While whole-chromosome paints may identify the origin of markers or detect translocations, arm-specific libraries will permit detailed analysis of chromosomal rearrangements when more precise information may be needed.

Adolescent↗
PubMed1993

Clinical and molecular evaluation of four patients with partial duplications of the long arm of chromosome 18.

Four individuals with partial duplications of the long arm of chromosome 18 were analyzed at the clinical, cytogenetic, and molecular levels. Two of the individuals had duplications of the long arm from 18q21.1-qter because of inheritance of an unbalanced translocation. Both of these individuals displayed the clinical phenotype characteristic of Edwards syndrome. Two other patients had de novo interstitial duplications of 18q but did not have a clinical diagnosis of Edwards syndrome. The extent of the duplicated material in each patient was determined initially by using cytogenetic analysis and subsequently with more detailed comparisons of the duplicated regions by using molecular probes derived from a chromosome 18-specific lambda phage library. The results demonstrated that one of the de novo interstitial duplications that did not result in the Edwards syndrome phenotype had a more proximal breakpoint than that of the partial duplications of the two patients with features of Edwards syndrome. These results suggest that a single critical region for Edwards syndrome in the proximal portion of 18q is unlikely.

Adolescent↗
PubMed1993

Molecular analysis of the 18q- syndrome--and correlation with phenotype.

Seven individuals with deletions of the distal long arm of chromosome 18 were evaluated at the clinical, cytogenetic, and molecular levels. The patients had varying degrees of typical clinical findings associated with the 18q- syndrome. Cytogenetic analysis revealed deletions from 18q21.3 or 18q22.2 to qter. Somatic cell hybrids derived from the patients were molecularly characterized using ordered groups of probes isolated from a chromosome 18-specific library. In general, the size of the deletion could be correlated with the severity of the phenotype. Based on the clinical pictures of these seven patients, a preliminary phenotypic map for the clinical features associated with deletions of the distal portion of the long arm has been generated. Furthermore, genes previously localized to 18q21 were mapped relative to the chromosome breakpoints present in these patients.

Abnormalities, Multiple↗
PubMed1992

Confirmation of a cryptic unbalanced translocation using whole chromosome fluorescence in situ hybridization.

We report on a 7-year-old boy with minor anomalies, growth retardation, and developmental delay with an initial 46,XY,der(18)t(18;?)(q23;?) chromosome constitution. To determine the origin of the additional chromosome segment, several candidate regions were identified including 4q and 18q. Clinical comparison showed more similarities to individuals with partial dup(4q) than to those with a dup(18q). Whole chromosome fluorescence in situ hybridization (FISH) was used to demonstrate the correct origin of the translocated region, clarifying the karyotype as 46,XY,der(18)t(4;18)(q28.2;q22.2), thus generating information of clinical importance. This illustrates the use of whole chromosome FISH to identify chromosome regions that cannot be determined conclusively using standard cytogenetic banding techniques.

Child↗