The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Gudrun A Rappold - One of the best experts on this subject based on the ideXlab platform.
-
molecular studies of an x y translocation chromosome in a woman with deletion of the Pseudoautosomal Region but normal height
Clinical Genetics, 2008Co-Authors: Stephanie Spranger, Katrin Schiebel, Annelyse Mertz, Stefan Kirsch, Gholamali Tariverdian, Gudrun A RappoldAbstract:: A translocation chromosome in a woman with the karyotype 46,X,der(X)t(X;Y)(p22.3; q11.2) was investigated by FISH and STS analysis with molecular probes derived from the sex chromosomes. Due to the partial deletion of the short arm Pseudoautosomal Region (PAR1) from DXYS14 to DXYS147 in the translocation chromosome, the proband is hemizygous for the gene responsible for growth control (SS) located in this Region, yet does not show growth retardation. Molecular analysis of the Yq arm of the translocation chromosome revealed the presence of markers DYS273 to DYS246 harboring the hypothesized growth control gene critical Region (GCY) on Yq, thereby placing the deletion breakpoint between markers DYS11 and DYS273. These results suggest that the Y-specific growth gene GCY on Yq compensates for the missing growth gene SS on Xp22.3.
-
evidence for heterogeneity in recombination in the human Pseudoautosomal Region high resolution analysis by sperm typing and radiation hybrid mapping
American Journal of Human Genetics, 2000Co-Authors: Sigbjorn Lien, Gudrun A Rappold, Joanna Szyda, Birgit Schechinger, Norm ArnheimAbstract:Accurate genetic and physical maps for the human Pseudoautosomal Region were constructed by use of sperm typing and high-resolution radiation-hybrid mapping. PCR analysis of 1,912 sperm was done with a manual, single-sperm isolation method. Data on four donors show highly significant linkage heterogeneity among individuals. The most significant difference was observed in a marker interval located in the middle of the Xp/Yp Pseudoautosomal Region, where one donor showed a particularly high recombination fraction. Longitudinal models were fitted to the data to test whether linkage heterogeneity among donors was significant for multiple intervals across the Region. The results indicated that increased recombination in particular individuals and Regions is compensated for by reduced recombination in neighboring intervals. To investigate correspondence between physical and genetic distances within the Region, we constructed a high-resolution radiation-hybrid map containing 29 markers. The recombination fraction per unit of physical distance varies between Regions ranging from 13- to 70-fold greater than the genome-average rate.
-
elevated dna sequence diversity in the genomic Region of the phosphatase ppp2r3l gene in the human Pseudoautosomal Region
Cytogenetic and Genome Research, 2000Co-Authors: Katrin Schiebel, Christine Fischer, J Meder, Andreas Rump, Andre Rosenthal, Martina Winkelmann, T Bonk, Andreas Humeny, Gudrun A RappoldAbstract:The evolution, inheritance and recombination rate of genes located in the Pseudoautosomal Region 1 (PAR1) is exceptional within the human genome. Pseudoautosomal genes are identical on X and Y chromosomes and are not inherited in a sex linked manner. Due to an obligatory recombination event in male meiosis, Pseudoautosomal genes are exchanged frequently between X and Y chromosomes. During the isolation, characterization and sequencing of a novel gene PPP2R3L, which was classified by sequence homology as a novel member of the protein phosphatase regulatory subunit families, it became apparent that cosmids of different origin harboring this gene are highly polymorphic between individuals, both at the nucleotide level and in the number and sequence of tandem repeats.
-
gene duplications as a recurrent theme in the evolution of the human Pseudoautosomal Region 1 isolation of the gene asmtl
Human Molecular Genetics, 1998Co-Authors: Katrin Schiebel, Karin Ried, Gudrun A RappoldAbstract:: We have isolated a novel gene, ASMTL (acetylserotonin methytransferase-like ), in the Pseudoautosomal Region (PAR1) on the human sex chromosomes. ASMTL represents a unique fusion product of two different full-length genes of different evolutionary origin and function. One part is homologous to the bacterial maf/orfE genes. The other part shows significant homology to the entire open reading frame of the previously described Pseudoautosomal gene ASMT, encoding the enzyme catalysing the last step in the synthesis of melatonin. We have also detected the identity of one exon (1A) of ASMT to exon 3 in yet another Pseudoautosomal gene, XE7. The data presented suggest that exon duplication and exon shuffling as well as gene fusion may represent common characteristics in the Pseudoautosomal Region.
-
genes located in and near the human Pseudoautosomal Region are located in the x y pairing Region in dog and sheep
Chromosome Research, 1997Co-Authors: Roland Toder, Gudrun A Rappold, Katrin Schiebel, Birgitta Glaser, Stephen A Wilcox, Jennifer Marshall A Graves, Werner SchemppAbstract:We cloned and mapped the dog and/or sheep homologues of two human Pseudoautosomal genes CSF2RA and ANT3. We also cloned and mapped dog and/or sheep homologues of STS and PRKX, which are located nearby on the differential Region of the human X and have related genes or pseudogenes on the Y. STS, as well as CSF2RA, mapped to the tips of the short arm of the sheep X and Y (Xp and Yp), and STS and PRKX, as well as ANT3, mapped to the tips of the dog Xp and Y long arm (Yq). These locations within the X-Y pairing Regions suggest that the Regions containing all these human Xp22.3-Xpter genes are Pseudoautosomal in dog and sheep. This supports the hypothesis that a larger Pseudoautosomal Region (PAR) shared by eutherian groups was disrupted by chromosomal rearrangements during primate evolution. The absence of STS and ANT3 from the sex chromosomes in two prosimian lemur species must therefore represent a recent translocation from their ancestral PAR, rather than retention of a smaller ancestral PAR shared by mouse.
Howard J Cooke - One of the best experts on this subject based on the ideXlab platform.
-
high frequency de novo alterations in the long range genomic structure of the mouse Pseudoautosomal Region
Nature Genetics, 1996Co-Authors: David Kipling, Eduardo Salido, Larry J Shapiro, Howard J CookeAbstract:High frequency de novo alterations in the long–range genomic structure of the mouse Pseudoautosomal Region
-
High frequency de novo alterations in the long–range genomic structure of the mouse Pseudoautosomal Region
Nature Genetics, 1996Co-Authors: David Kipling, Eduardo Salido, Larry J Shapiro, Howard J CookeAbstract:High frequency de novo alterations in the long–range genomic structure of the mouse Pseudoautosomal Region
-
structural variation of the Pseudoautosomal Region between and within inbred mouse strains
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: David Kipling, Helen Wilson, Eric J Thomson, Jo K Perry, Stephen J Palmer, Alan Ashworth, Howard J CookeAbstract:The Pseudoautosomal Region (PAR) is a segment of shared homology between the sex chromosomes. Here we report additional probes for this Region of the mouse genome. Genetic and fluorescence in situ hybridization analyses indicate that one probe, PAR-4, hybridizes to the Pseudoautosomal telomere and a minor locus at the telomere of chromosome 9 and that a PCR assay based on the PAR-4 sequence amplifies only the Pseudoautosomal locus (DXYHgu1). The Region detected by PAR-4 is structurally unstable; it shows polymorphism both between mouse strains and between animals of the same inbred strain, which implies an unusually high mutation rate. Variation occurs in the Region adjacent to a (TTAGGG)n array. Two Pseudoautosomal probes can also hybridize to the distal telomeres of chromosomes 9 and 13, and all three telomeres contain DXYMov15. The similarity between these telomeres may reflect ancestral telomere-telomere exchange.
Larry J Shapiro - One of the best experts on this subject based on the ideXlab platform.
-
high frequency de novo alterations in the long range genomic structure of the mouse Pseudoautosomal Region
Nature Genetics, 1996Co-Authors: David Kipling, Eduardo Salido, Larry J Shapiro, Howard J CookeAbstract:High frequency de novo alterations in the long–range genomic structure of the mouse Pseudoautosomal Region
-
High frequency de novo alterations in the long–range genomic structure of the mouse Pseudoautosomal Region
Nature Genetics, 1996Co-Authors: David Kipling, Eduardo Salido, Larry J Shapiro, Howard J CookeAbstract:High frequency de novo alterations in the long–range genomic structure of the mouse Pseudoautosomal Region
-
role of the Pseudoautosomal Region in sex chromosome pairing during male meiosis meiotic studies in a man with a deletion of distal xp
American Journal of Human Genetics, 1992Co-Authors: T Mohandas, R M Speed, Merry Passage, A C Chandley, Larry J ShapiroAbstract:Meiotic studies were undertaken in a 24-year-old male patient with short stature, chondrodysplasia punctata, ichthyosis, steroid sulfatase deficiency, and mild mental retardation with an inherited cytologically visible deletion of distal Xp. Molecular investigations showed that the Pseudoautosomal Region as well as the steroid sulfatase gene were deleted, but telomeric sequences were present at the pter on the deleted X chromosome. A complete failure of sex-chromosome pairing was observed in the primary spermatocytes of the patient. Telomeric approaches between the sex chromosomes were made at zygotene in some cells, but XY synaptonemal complex was formed. The sex chromosomes were present as univalents at metaphase I, and germ-cell development was arrested between metaphase I and metaphase II in the vast majority of cells, consistent with the azoospermia observed in the patient. The failure of XY pairing in this individual indicates that the Pseudoautosomal sequences play an important role in initiating XY pairing and formation of synaptonemal complex at meiosis. 36 refs., 6 figs.
Christine Fischer - One of the best experts on this subject based on the ideXlab platform.
-
elevated dna sequence diversity in the genomic Region of the phosphatase ppp2r3l gene in the human Pseudoautosomal Region
Cytogenetic and Genome Research, 2000Co-Authors: Katrin Schiebel, Christine Fischer, J Meder, Andreas Rump, Andre Rosenthal, Martina Winkelmann, T Bonk, Andreas Humeny, Gudrun A RappoldAbstract:The evolution, inheritance and recombination rate of genes located in the Pseudoautosomal Region 1 (PAR1) is exceptional within the human genome. Pseudoautosomal genes are identical on X and Y chromosomes and are not inherited in a sex linked manner. Due to an obligatory recombination event in male meiosis, Pseudoautosomal genes are exchanged frequently between X and Y chromosomes. During the isolation, characterization and sequencing of a novel gene PPP2R3L, which was classified by sequence homology as a novel member of the protein phosphatase regulatory subunit families, it became apparent that cosmids of different origin harboring this gene are highly polymorphic between individuals, both at the nucleotide level and in the number and sequence of tandem repeats.
-
Double crossover in the human Xp/Yp Pseudoautosomal Region and its bearing on interference
Human Molecular Genetics, 1994Co-Authors: Gudrun A Rappold, Albrecht Klink, Blrglt Weiss, Christine FischerAbstract:Most models on crossover and crossover interference have assumed that the intensity of interference depends inversely on the physical distance separating the respective intervals. The possibility, however, also exists that interference depends on genetic rather than on physical distance. As the human Pseudoautosomal Region (PAR) on Xp/Yp is physically small, yet genetically a hot spot of recombination in male meiosis, studies on the existence of multiple crossover events may be particularly useful in addressing the question of interference. Our results demonstrate for the first time a double crossover during male meiosis in the human PAR on Xp/Yp. The occurrence of a single obligatory recombination event in this Region can, therefore, no longer be taken as a dogma
-
double crossover in the human xp yp Pseudoautosomal Region and its bearing on interference
Human Molecular Genetics, 1994Co-Authors: Gudrun A Rappold, Albrecht Klink, Blrglt Weiss, Christine FischerAbstract:: Most models on crossover and crossover interference have assumed that the intensity of interference depends inversely on the physical distance separating the respective intervals. The possibility, however, also exists that interference depends on genetic rather than on physical distance. As the human Pseudoautosomal Region (PAR) on Xp/Yp is physically small, yet genetically a hot spot of recombination in male meiosis, studies on the existence of multiple crossover events may be particularly useful in addressing the question of interference. Our results demonstrate for the first time a double crossover during male meiosis in the human PAR on Xp/Yp. The occurrence of a single obligatory recombination event in this Region can, therefore, no longer be taken as a dogma. However, double crossover events seem to remain exceptional and, thus, the model originally suggested by Burgoyne remains globally correct. As both recombination events can be localized within a narrow range of physical distance, theories describing interference due to steric hindrance may have to be reconsidered. This finding may, therefore, have general implications for our understanding of the mechanism of positive and negative crossover interference in mammalian genomes and may be interesting especially for linkage mapping where double recombinations in small intervals tend to be considered as genotyping errors.
-
genetic map of the human Pseudoautosomal Region reveals a high rate of recombination in female meiosis at the xp telomere
Genomics, 1993Co-Authors: Anja Henke, Christine Fischer, Gudrun A RappoldAbstract:This paper describes the genetic map of the Pseudoautosomal Region bounded by the telomere of the short arms of the X and Y chromosomes. In males, meiotic exchange on Xp/Yp is confined to this Region, leading to highly elevated recombination rates. The map was constructed using 11 Pseudoautosomal probes (six of which are new) and typing individuals from 38 CEPH families. All markers have been physically mapped, thus providing the opportunity to compare genetic distance to physical distance through all intervals of the map. This comparison reveals an unexpected high rate of recombination in female meiosis between loci DXYS20 and DXYS78, within 20–80 kb from the telomere. Within this telomere-adjacent Region no differences in male and female recombination rates are seen. Furthermore, data from this genetic map support the hypothesis of a linear gradient of recombination across most of the Region in male meiosis and provide densely spaced anchor points for linkage studies especially in the telomeric portion of the Pseudoautosomal Region.
Tsutomu Ogata - One of the best experts on this subject based on the ideXlab platform.
-
compound heterozygous deletions in Pseudoautosomal Region 1 in an infant with mild manifestations of langer mesomelic dysplasia
American Journal of Medical Genetics Part A, 2014Co-Authors: Takayoshi Tsuchiya, Tsutomu Ogata, Minoru Shibata, Hironao Numabe, Tomoko Jinno, Kazuhiko Nakabayashi, Gen Nishimura, Toshiro Nagai, Maki FukamiAbstract:Haploinsufficiency of SHOX on the short arm Pseudoautosomal Region (PAR1) leads to Leri–Weill dyschondrosteosis (LWD), and nullizygosity of SHOX results in Langer mesomelic dysplasia (LMD). Molecular defects of LWD/LMD include various microdeletions in PAR1 that involve exons and/or the putative upstream or downstream enhancer Regions of SHOX, as well as several intragenic mutations. Here, we report on a Japanese male infant with mild manifestations of LMD and hitherto unreported microdeletions in PAR1. Clinical analysis revealed mesomelic short stature with various radiological findings indicative of LMD. Molecular analyses identified compound heterozygous deletions, that is, a maternally inherited ∼46 kb deletion involving the upstream Region and exons 1–5 of SHOX, and a paternally inherited ∼500 kb deletion started from a position ∼300 kb downstream from SHOX. In silico analysis revealed that the downstream deletion did not affect the known putative enhancer Regions of SHOX, although it encompassed several non-coding elements which were well conserved among various species with SHOX orthologs. These results provide the possibility of the presence of a novel enhancer for SHOX in the genomic Region ∼300 to ∼800 kb downstream of the start codon. © 2013 Wiley Periodicals, Inc.
-
Compound heterozygous deletions in Pseudoautosomal Region 1 in an infant with mild manifestations of langer mesomelic dysplasia.
American journal of medical genetics. Part A, 2013Co-Authors: Takayoshi Tsuchiya, Tsutomu Ogata, Minoru Shibata, Hironao Numabe, Tomoko Jinno, Kazuhiko Nakabayashi, Gen Nishimura, Toshiro Nagai, Maki FukamiAbstract:Haploinsufficiency of SHOX on the short arm Pseudoautosomal Region (PAR1) leads to Leri-Weill dyschondrosteosis (LWD), and nullizygosity of SHOX results in Langer mesomelic dysplasia (LMD). Molecular defects of LWD/LMD include various microdeletions in PAR1 that involve exons and/or the putative upstream or downstream enhancer Regions of SHOX, as well as several intragenic mutations. Here, we report on a Japanese male infant with mild manifestations of LMD and hitherto unreported microdeletions in PAR1. Clinical analysis revealed mesomelic short stature with various radiological findings indicative of LMD. Molecular analyses identified compound heterozygous deletions, that is, a maternally inherited ∼46 kb deletion involving the upstream Region and exons 1-5 of SHOX, and a paternally inherited ∼500 kb deletion started from a position ∼300 kb downstream from SHOX. In silico analysis revealed that the downstream deletion did not affect the known putative enhancer Regions of SHOX, although it encompassed several non-coding elements which were well conserved among various species with SHOX orthologs. These results provide the possibility of the presence of a novel enhancer for SHOX in the genomic Region ∼300 to ∼800 kb downstream of the start codon.
-
fish deletion mapping defines a 270 kb short stature critical interval in the Pseudoautosomal Region par1 on human sex chromosomes
Human Genetics, 1997Co-Authors: Birgit Weiss, Katrin Schiebel, Annelyse Mertz, J Meder, Maki Fukami, Tsutomu Ogata, U Heinrich, J Garciaheras, Gudrun A RappoldAbstract:Deletions of the Pseudoautosomal Region (PAR1) of the sex chromosomes have recently been discovered in individuals with short stature, and a minimal common deletion Region of 700 kb within PAR1 has subsequently been defined. We have cloned this entire Region, which is bounded by the Xp/Yp telomere, as an overlapping cosmid contig. In the present study, we have used fluorescence in situ hybridization (FISH) to study four patients with X-chromosomal rearrangements, two with normal height and two with short stature. Genotype-phenotype correlations have narrowed down the the critical “short stature interval” to a 270-kb Region containing the gene with an important role in growth. A minimal tiling path of 6–8 cosmids bridging this interval is now available for interphase and metaphase FISH and provides a valuable tool for diagnostic investigations of patients with idiopathic short stature.
-
short stature in a girl with partial monosomy of the Pseudoautosomal Region distal to dxys15 further evidence for the assignment of the critical Region for a Pseudoautosomal growth gene s
Journal of Medical Genetics, 1995Co-Authors: Tsutomu Ogata, Gudrun A Rappold, N Matsuo, Atsuko Yoshizawa, Koji Muroya, Yoshimitsu Fukushima, Susumu YokoyaAbstract:This report describes a 12 year 10 month old girl with short stature and a non-mosaic 46,X,Xp+ karyotype. Her height remained below −2 SD of the mean, and her predicted adult height (143 cm) was below her target height (155·5 cm) and target range (147·5 cm−163·5 cm). Cytogenetic and molecular studies showed that the Xp+ chromosome was formed by an inverted duplication of the Xp21.3−Xp22.33 segment and was missing about 700 kb of DNA from the Pseudoautosomal Region distal to DXYS15. The results provide further support for the previously proposed hypothesis that the Region between DXYS20 and DXYS15 is the critical Region for a Pseudoautosomal growth gene(s).
-
short stature in a girl with a terminal xp deletion distal to dxys15 localisation of a growth gene s in the Pseudoautosomal Region
Journal of Medical Genetics, 1992Co-Authors: Tsutomu Ogata, Peter N Goodfellow, Christine Petit, N MatsuoAbstract:Abstract This report describes a Japanese girl with short stature and a rearranged X chromosome. Her height remained below the 3rd centile growth curve for Japanese girls, and her predicted adult height (148.5 cm) was below her target height (163 cm) and target range (155 to 171 cm). Cytogenetic studies showed that the rearranged X chromosome was formed by a breakage at q26 and a transfer of the Xq fragment onto the tip of Xp. The abnormal X was always late replicating. No mosaicism was detected. Molecular analysis showed an Xp terminal deletion distal to DXYS15. Biochemical and radiological studies for short stature disclosed no abnormality. On the basis of height analysis of previous reports and a genotype-phenotype correlation of this patient, we propose that a growth gene(s) is present in the distal part of the Pseudoautosomal Region.
