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Biomedical subjects

W Schempp

Publications and source records attributed to W Schempp.

At least 55 records · Page 3Linked to original sources
PubMed1994

Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9.

A human autosomal XY sex reversal locus, SRA1, associated with the skeletal malformation syndrome campomelic dysplasia (CMPD1), has been placed at distal 17q. The SOX9 gene, a positional candidate from the chromosomal location and expression pattern reported for mouse Sox9, was isolated and characterized. SOX9 encodes a putative transcription factor structurally related to the testis-determining factor SRY and is expressed in many adult tissues, and in fetal testis and skeletal tissue. Inactivating mutations on one SOX9 allele identified in nontranslocation CMPD1-SRA1 cases point to haploinsufficiency for SOX9 as the cause for both campomelic dysplasia and autosomal XY sex reversal. The 17q breakpoints in three CMPD1 translocation cases map 50 kb or more from SOX9.

Amino Acid Sequence↗
PubMed1994

Evolution of the chAB4 multisequence family in primates.

Approximately 50 members of the primate-specific multisequence family chAB4 are located as clusters at eight different chromosomal loci within the human genome. The whole cloned region of chAB4 represents a single-copy or low-copy sequence in all nonhuman primates tested, with the exception of the chimpanzee, for which we found chAB4 copy numbers similar to those in the human. An Alu element was inserted into chAB4 after the divergence of the Old World monkeys from the hominoids but before chAB4 was amplified. The first amplification step could be dated after the great apes and the human diverged from the Old World monkeys. We have evidence that neither the copy numbers nor the chromosomal locations remained stable after this initial step and that gross alterations in the relative copy numbers of individual family members occurred even after the divergence of the human and the chimpanzee. Taken together, our data suggest that chAB4, in an evolutionary sense, is an unusually unstable sequence family.

Animals↗
PubMed1994

De novo isochromosome 18p in two patients: cytogenetic diagnosis and confirmation by chromosome painting.

This report concerns two patients with clinical features typical for tetrasomy 18p syndrome. Chromosomal analysis revealed a male karyotype in both cases, with an additional small metacentric marker chromosome, putatively an i(18p). Fluorescent in situ hybridization with a chromosome 18-specific paint confirmed that the marker chromosome consisted of chromosome 18 material in both cases.

Abnormalities, Multiple↗
PubMed1993

Comparative mapping of SRY in the great apes.

Cytogenetic studies of the primate Y chromosomes have suggested that extensive rearrangements have occurred during evolution of the great apes. We have used in situ hybridization to define these rearrangements at the molecular level. pHU-14, a probe including sequences from the sex determining gene SRY, hybridizes close to the early replicating pseudoautosomal segment in a telomeric or subtelomeric position of the Y chromosomes of all great apes. The low copy repeat detected by the probe Fr35-II is obviously included in Y chromosomal rearrangements during hominid evolution. These results, combined with previous studies, suggest that the Y chromosome in great apes has a conserved region including the pseudoautosomal region and the testis-determining region. The rest of the Y chromosome has undergone several rearrangements in the different great apes.

Animals↗
PubMed1993

Inverted and satellited Y chromosome in the orangutan (Pongo pygmaeus).

An inverted and satellited Y chromosome of almost acrocentric appearance was detected in seven of 14 male orangutans. In the remaining seven animals a submetacentric Y chromosome without NORs occurred. The high frequency with which the satellited Y chromosomes were associated with acrocentric autosomes and the positive AgNO3-staining of their satellite stalks clearly indicate the active state of the NOR on the Y chromosomes. DNA fingerprinting in two orangutan families showed that the inverted and satellited Y chromosomes in carrier orangutan males do not interfere with normal fertility. Within our sample of male orangutans studied, the inverted and satellited Y chromosome is restricted to Sumatran animals; all Bornean specimens possessed the submetacentric Y chromosome. The question arises whether these two kinds of Y chromosome differ constitutively between the Pongo pygmaeus subpopulations.

Animals↗
PubMed1993

Assignment of an autosomal sex reversal locus (SRA1) and campomelic dysplasia (CMPD1) to 17q24.3-q25.1.

We have mapped the autosomal sex reversal locus, SRA1, associated with campomelic dysplasia (CMPD1) to 17q24.3-q25.1 by three independent apparently balanced de novo reciprocal translocations. Chromosome painting indicates that the translocated segment of 17q involves about 15% of chromosome 17 in all three translocations, corresponding to a breakpoint at the interphase between 17q24-q25. All three 17q breakpoints were localized distal to the growth hormone locus (GH), and proximal to thymidine kinase (TK1). Due to the distal location of the breakpoints, previously mentioned candidate genes, HOX2 and COL1A1, can be excluded as being involved in CMPD1/SRA1. The mouse mutant tail-short (Ts) which maps to the homologous syntenic region on mouse chromosome 11, displays some of the features of CMPD1.

Abnormalities, Multiple↗
PubMed1993

A retrospective CISS hybridization analysis of a case with de novo translocation t(18;22) resulting in an 18p- syndrome.

An unbalanced de novo translocation t(18;22) leading to a severely malformed liveborn girl with 18p- syndrome is described. Using the chromosomal in situ suppression (CISS) hybridization technique on 4-year-old G-banded chromosome preparations, it could be demonstrated that the translocation chromosome is composed of the long arm including the centromere of a chromosome 22 and the long arm of a chromosome 18. Consequently, the patient described here has lost the short arm including the centromere of chromosome 18. The possibility of restudying cytogenetically unsolved cases in clinical cytogenetics using older G-banded chromosome preparations with the fluorescence in situ hybridization techniques is pointed out.

Adult↗
PubMed1993

An X-Y homologous pairing segment in tree shrews (Tupaia).

High-resolution early replication banding of tupaia metaphase chromosomes revealed a synchronous early replicating segment in the short-arm telomeric regions of the active and inactive X chromosomes and in the long-arm telomeric region of the Y chromosome. Hybridization with the human-derived pseudoautosomal probe 113F (STIR) showed that this repeat is conserved and specifically localized within these synchronously early replicating segments of the X short arm and the Y long arm of all three tupaia species (Tupaia belangeri, T. chinensis, and T. glis) investigated. Moreover, meiotic studies demonstrated that a synaptonemal complex is formed at one telomeric end of the XY bivalent during the pachytene stage of meiosis in a male T. glis specimen. Thus, apart from the mouse, the tupaias are the first nonprimate mammals for which cytogenetic and molecular evidence is provided that their highly heteromorphic X and Y chromosomes share a conserved homologous segment in the telomeric position, a location that is compatible with pairing and crossing-over in male meiosis. Taken together, these observations strongly, albeit indirectly, suggest that this chromosome segment at the tip of a sex-chromosome arm might behave pseudoautosomally.

Animals↗
PubMed1992

Comparative cytogenetic studies in tree shrews (Tupaia).

Through use of BrdU replication, RBA-banded karyotypes of Tupaia belangeri, T. chinensis, and T. glis were obtained. A chromosome number of 2n = 62 for T. belangeri is described here for the first time and is confirmed for T. chinensis. All chromosomes between these two phenotypically different species appear to have identical RBA banding patterns; in addition, there is no difference between T. belangeri and T. chinensis in the number and position of nucleolus organizer regions (NORs). The reduced chromosome number of 2n = 60 in T. glis can be explained by a Robertsonian translocation between two acrocentric chromosome pairs, Nos. 10 and 13, of T. belangeri and/or T. chinensis, resulting in the metacentric chromosome pair 1 of T. glis. Furthermore, two chromosome pairs each of T. glis and T. belangeri and/or T. chinensis are not homoeologous, as judged by their RBA patterns. Differences were also found in the number and position of NORs; whereas T. glis displays eight positively stained NORs after AgNO3 staining, there are only four silver-stained NORs in both T. belangeri and T. chinensis. The possibility of geographical isolation as an explanation for the lack of chromosomal differentiation between T. belangeri and T. chinensis is discussed.

Animals↗
PubMed1991

Homozygous condition for a BrdU-requiring fragile site on chromosome 12.

A rare BrdU-sensitive fragile site, designated FRA12C*RQ24.2 has a relatively high frequency in the normal population. It can be demonstrated in a heterozygous and homozygous condition. There is no evidence that a phenotypic abnormality is associated with the expression of this site. A comparison with the fragile site FRA10B*RQ25.2 has revealed common features with FRA12C*RQ24.2.

Bromodeoxyuridine↗
PubMed1991

Comparative mapping of ZFY in the hominoid apes.

Within our project of comparative mapping of candidate genes for sex-determination/testis differentiation, we used a cloned probe from the human ZFY locus for comparative hybridization studies in hominoids. As in the human, the ZFY probe detects X- and Y-specific restriction fragments in the chimpanzee, the gorilla, the orangutan, and the gibbon. Furthermore, the X-specific hybridization site in the great apes resides in Xp21.3, the same locus defining ZFX in the human. The Y-specific locus of ZFY maps closely to the early replicating pseudoautosomal segment in the telomeric or subtelomeric position of the Y chromosomes of the great apes, again as found in the human. Thus, despite cytogenetically visible structural alterations within the euchromatic parts of the Y chromosomes of the human species and the great apes, a segment of the Y chromosome defined by the pseudoautosomal region and ZFY seems to be more strongly conserved than the rest of the Y chromosome.

Animals↗
PubMed1990

The human pregnancy-specific glycoprotein genes are tightly linked on the long arm of chromosome 19 and are coordinately expressed.

The pregnancy-specific glycoprotein (PSG) genes encode a group of proteins which are found in large amounts in placenta and maternal serum. In situ hybridization analyses of metaphase chromosomes reveal that all the human pregnancy-specific glycoprotein (PSG) genes are located on the long arm of chromosome 19 (19q13.2-13.3), overlapping the region containing the closely-related carcinoembryonic antigen (CEA) gene subgroup. Higher resolution analyses indicate that the PSG genes are closely linked within an 800kb SacII restriction endonuclease fragment. This has been confirmed through restriction endonuclease mapping and DNA sequence analyses of isolated genomic clones, which show that at least some of these genes are located in very close proximity. Further, these studies have helped to identify a new member of the PSG gene subfamily (PSG7). DNA/RNA hybridization analyses, using gene-specific oligonucleotide probes based on published sequences, showed that five from six PSG genes tested are coordinately transcribed in the placenta. Due to the close proximity of these genes and their coordinated expression pattern, common transcriptional regulatory elements may exist.

Base Sequence↗
PubMed1990

Chromosome abnormalities in multiple meningiomas of a child.

We report the cytogenetic findings in two meningiomas from a child presenting with multiple meningiomas. In contrast to the chromosomal profile of adult meningiomas, both tumors studied revealed excess of chromosomes in addition to monosomy 22. This difference is remarkable considering several reports indicating that childhood meningiomas behave differently and have a worse prognosis than those in adults.

Aneuploidy↗
PubMed1990

[Diagnosis of multiple endocrine neoplasms type IIa using DNA analysis].

The gene causing MEN IIa has recently being assigned to the pericentromeric region of chromosome 10. We performed linkage analysis using DNA-markers closely related to the chromosomal locus at chromosome 10: MCK II, retinol binding protein cDNA and cTBIRBP-9. Available for the study were EDTA blood from two families. The analysis was positive in two asymptomatic offsprings in one family (B), whereas the markers were not informative in the other family (A). Genetic distance of the informative marker of family A to MEN IIa gene is 2 cM, i.e. a likelihood of 98% (95% up a confidence limit with 5%) for the gene carrier status of two children aged 11 and 7 y old. The following clinical investigation including pentagastrin test, plasma catecholamines and 24 hour urine catecholamines and parathormone was negative until now. We recommend early linkage analysis for establishing the genetic status in offspring of MEN IIa families to focus further screening to those, who are predicted to be gene carrier.

DNA, Neoplasm↗
PubMed1989

Early diagnosis of multiple endocrine neoplasia type IIa.

We report on incidental findings during family screening of two kindreds with multiple endocrine neoplasia type IIa. Pheochromocytoma and medullary thyroid carcinoma of considerable size were detected. The results underline the importance of early diagnosis of the syndrome, since the afflicted may be almost or wholly asymptomatic. High resolution chromosome banding studies were carried out in both families, but no abnormality was found. Linkage analysis using DNA markers closely related to the chromosomal locus at chromosome 10 was carried out and was positive in two asymptomatic offspring of one family, whereas the markers were not informative in a second family. We recommend early linkage analysis for establishing the genetic status in offspring of multiple endocrine neoplasia type IIa families to identify for further screening those who are predicted to be gene carrier.

Adrenal Gland Neoplasms↗
PubMed1989

Analysis of two 47,XXX males reveals X-Y interchange and maternal or paternal nondisjunction.

Two cases of 47,XXX males were studied, one of which has been published previously (Bigozzi et al. 1980). Analysis of X-linked restriction fragment length polymorphisms revealed that in this case, one X chromosome was of paternal and two were of maternal origin, whereas in the other case, two X chromosomes were of paternal and one of maternal origin. Southern blot analysis with Y-specific DNA probes demonstrated the presence of Y short arm sequences in both XXX males. In one case, the results obtained pointed to a paracentric inversion on Yp of the patient's father. In situ hybridization indicated that the Y-specific DNA sequences were localized on Xp22.3 in one of the three X chromosomes in both cases. The presence of Y DNA had no effect on random X inactivation. It is concluded that both XXX males originate from aberrant X-Y interchange during paternal meiosis, with coincident nondisjunction of the X chromosome during maternal meiosis in case 1, and during paternal meiosis II in case 2.

Adolescent↗
PubMed1989

Duplication of an Xp segment that includes the ZFX locus causes sex inversion in man.

Two 46,XY females with tandem duplications of an X short arm segment were studied by cytogenetic and Southern blot analysis. The results show that the duplicated segment in each case included the Xp21.2-Xp22.2 interval, resulting in a double dose of ZFX on the single active X chromosome. The results from our two cases, in conjunction with those reported by other workers, lead us to conclude that the duplication is the reason for the sex inversion. If ZFY and ZFX are indeed sex-determining gene loci, these findings favour a model of sex determination characterized by antagonistic interaction between these genes.

Chromosome Banding↗