ABSTRACT
Intensive active surveillance has uncovered two atypical German BSE cases in older cattle which resemble the two different atypical BSE phenotypes that have recently been described in France (designated H-type) and Italy (designated L-type or BASE). The H-type is characterized by a significantly higher molecular size, but a conventional glycopattern of the proteinase K treated abnormal prion protein (PrP(Sc)), while the L-type PrP(Sc) has only a slightly lower molecular size and a distinctly different glycopattern. In this paper we describe the successful transmission of both German atypical BSE cases to transgenic mice overexpressing bovine PrP(C). Upon challenge with the L-type, these mice developed BSE after a substantially shorter incubation period than any classical BSE transmission using these mice to date. In contrast, the incubation period was distinctly prolonged when these mice were challenged with the H-type. PrP(Sc) accumulated in the brains of these mice were of the same atypical BSE type that had been used for the transmission. These atypical cases suggest the possible existence of sporadic BSE cases in bovines. It is thus feasible that the BSE epidemic in the UK could have also been initiated by an intraspecies transmission from a sporadic BSE case.
Subject(s)
Encephalopathy, Bovine Spongiform/transmission , PrPC Proteins/chemistry , PrPC Proteins/pathogenicity , PrPSc Proteins/chemistry , PrPSc Proteins/pathogenicity , Amino Acid Sequence , Animals , Brain/metabolism , Cattle , Disease Susceptibility , Encephalopathy, Bovine Spongiform/metabolism , Endopeptidase K/metabolism , Germany , Immunohistochemistry/veterinary , Mice , Mice, Transgenic , Molecular Sequence Data , Molecular Weight , Polymerase Chain Reaction/methods , Polymerase Chain Reaction/veterinary , PrPC Proteins/metabolism , PrPSc Proteins/metabolism , Time FactorsABSTRACT
Polymorphisms of the prion protein gene PRNP have been shown to influence the susceptibility/resistance to prion infections in human and sheep. In addition, the T174M polymorphism within the flanking prion doppel gene (PRND) was thought to be involved in susceptibility to sporadic Creutzfeldt-Jacob disease. To study a possible influence of DNA polymorphisms of the bovine PRND gene in bovine spongiform encephalopathy (BSE), previously identified and newly isolated DNA polymorphisms were genotyped in all available German cattle that tested positive for BSE. Genotypes and calculated haplotypes were compared with breeding bulls serving as controls. Analysis of the four major breeds Schwarzbunt (Holstein Friesian), Rotbunt (Holstein Red), Fleckvieh (Simmental), and Braunvieh (Swiss Brown) resulted in the isolation of the previously known polymorphisms R50H and R132Q and two novel synonymous single nucleotide polymorphisms (SNPs) C4820T and A5063T. Comparative genotype and haplotype analysis of BSE and control animals revealed a significantly different distribution of polymorphisms C4815T and R132Q in Fleckvieh animals but not in the other breeds tested. No association to BSE susceptibility was detectable for polymorphisms R50H and A5063T.
Subject(s)
DNA/genetics , Encephalopathy, Bovine Spongiform/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Genetic , Prions/genetics , Amyloid/genetics , Animals , Cattle , Genotype , Haplotypes , Polymorphism, Single Nucleotide , Prion Proteins , Protein Precursors/genetics , Species Specificity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
GABA (gamma-aminobutyric acid) is a major inhibitory neurotransmitter in the central nervous system (CNS) which activates both ionotropic (GABA(A)/GABA(C)) and metabotropic (GABA(B)) receptor systems. We identified two alternatively spliced cDNA variants of the murine GABA(B) receptor 1 that are predominantly expressed in the CNS. Deduced protein structures are highly homologous to the previously characterized rat and human receptors. Comparison of the genomic structures of mouse and human revealed that alternative splicing occurred at the same position, whereas the mouse gene has an additional 5' exon. Radiation hybrid mapping, combined with database searches, indicated that the GABA(B) receptor gene (Gabbr1) is located on mouse chromosome 17, adjacent to the marker D17Mit24 in a region homologous to human chromosome 6p21.3.
Subject(s)
Alternative Splicing/genetics , Gene Expression Profiling , Radiation Hybrid Mapping , Receptors, GABA-B/genetics , Amino Acid Sequence , Animals , Base Sequence , Central Nervous System/metabolism , Cloning, Molecular , DNA, Complementary/genetics , Databases as Topic , Exons/genetics , Expressed Sequence Tags , Humans , Introns/genetics , Mice , Molecular Sequence Data , RNA, Messenger/analysis , RNA, Messenger/genetics , Rats , Receptors, GABA , Receptors, GABA-A , Receptors, GABA-B/chemistryABSTRACT
Structural abnormalities of chromosome 18p mainly consist of isochromosomes of the short arm, which result in tetrasomy 18p. Trisomy 18p is much rarer, and less well characterized. We report on a 12-year-old girl with minor facial anomalies, delayed development, abnormal hands, atopic dermatitis, and hearing loss. She was mosaic for two abnormal cell lines in peripheral blood. In 90% of cells, a dicentric chromosome with duplication of the whole short arm of chromosome 18 resulted in trisomy 18p; 10% of cells had monosomy 18p, arising from a t(14;18)(p11;q11). FISH mapping, with multiple region specific and locus specific probes from the short and long arm of chromosome 18, showed that the structure of the dicentric chromosome 18 was 18pter-->18q23::18q11-->18pter. DNA polymorphisms for chromosome 18 showed that the abnormalities of chromosome 18 were paternal in origin. Combining all results, we could link the trisomy 18p and monosomy 18p to a common origin via a complex series of events in an early mitosis.
Subject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 18/genetics , Abnormalities, Multiple/genetics , Adult , Child , Chromosomes, Human, Pair 14/genetics , DNA/genetics , Deafness , Dermatitis, Atopic , Family Health , Female , Humans , In Situ Hybridization, Fluorescence , Male , Monosomy , Mosaicism , Speech Disorders , Translocation, Genetic , TrisomyABSTRACT
Females with XY gonadal dysgenesis are sterile, due to degeneration of the initially present ovaries into nonfunctional streak gonads. Some of these sex-reversal cases can be attributed to mutation or deletion of the SRY gene. We now describe an SRY-deleted 47,XXY female who has one son and two daughters, and one of her daughters has the same 47,XXY karyotype. PCR and FISH analysis revealed that the mother carries a structurally altered Y chromosome that most likely resulted from an aberrant X-Y interchange between the closely related genomic regions surrounding the gene pair PRKX and PRKY on Xp22.3 and Yp11.2, respectively. As a consequence, Yp material, including SRY, has been replaced by terminal Xp sequences up to the PRKX gene. The fertility of the XXY mother can be attributed to the presence of the additional X chromosome that is missing in XY gonadal dysgenesis females. To our knowledge, this is the first human XXY female described who is fertile.
Subject(s)
DNA-Binding Proteins/genetics , Disorders of Sex Development/genetics , Nuclear Proteins , Sequence Deletion/genetics , Sex Chromosome Aberrations/genetics , Transcription Factors , X Chromosome/genetics , Y Chromosome/genetics , Female , Fertility/genetics , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Klinefelter Syndrome/diagnosis , Klinefelter Syndrome/genetics , Male , Nuclear Family , Pregnancy , Prenatal Diagnosis , Recombination, Genetic/genetics , Sex Chromosome Aberrations/diagnosis , Sex-Determining Region Y ProteinABSTRACT
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.
Subject(s)
Genetic Variation/genetics , Phosphoric Monoester Hydrolases/genetics , Polymorphism, Genetic/genetics , Sex Chromosomes/genetics , Amino Acid Sequence , Cloning, Molecular , Crossing Over, Genetic/genetics , DNA, Complementary/genetics , Dosage Compensation, Genetic , Gene Dosage , Gene Expression Profiling , Humans , Molecular Sequence Data , Phosphoric Monoester Hydrolases/chemistry , Protein Subunits , RNA, Messenger/analysis , RNA, Messenger/genetics , Sequence Alignment , Sequence Homology, Amino AcidABSTRACT
The three-dimensional positioning of the X-chromosomal adenine nucleotide translocase genes, ANT2 and ANT3, were compared in the active and inactive X chromosome territories (Xa and Xi) of female human amniotic fluid cell nuclei. ANT2 is located in Xq24-q25 and is transcriptionally active on Xa, but inactive on Xi. ANT3 is located in the pseudoautosomal region Xp22.3 and escapes X-inactivation. Three-color fluorescence in situ hybridization, confocal laser scanning microscopy, and three-dimensional image analysis revealed that transcriptionally active ANT2 and ANT3 genes were positioned more peripheral within their chromosome territory than the inactive ANT2 gene. The position of the latter was significantly more interior in the Xi territory. Although the volumes of both X territories were similar, 3D distances between ANT2 and ANT3 were significantly smaller in Xi compared to Xa territories reflecting different territory shapes. Our data show a correlation between 3D positioning and transcriptional activity of these X-specific genes.
Subject(s)
Mitochondrial ADP, ATP Translocases/genetics , X Chromosome , Amniotic Fluid , Cell Nucleus , Female , Gene Expression Regulation , Humans , In Situ Hybridization, Fluorescence , Microscopy, Confocal , Mitochondrial ADP, ATP Translocases/ultrastructure , Nucleic Acid Conformation , Pregnancy , X Chromosome/genetics , X Chromosome/ultrastructureABSTRACT
We have isolated the prosimian lemur homologues for STS and SRY. FISH unambiguously co-localized STS with SHOX, IL3RA, ANT3 and PRK into the meiotic X-Y pairing region (PAR) of lemurs. In contrast to the close proximity of SRY to the pseudoautosomal boundary (PAB) on the Y chromosome in simian primates, SRY maps distant from the PAR in lemurs. Most interestingly, we were able to determine a DNA sequence divergence of 12.5% between the human and lemur SRY HMG box. This divergence directs to a 52 million year period of separate evolution of human and lemur SRY genes. Phylogenetically, this time period falls in between the times that prosimians and New World monkeys branched from the human lineage. Thus, we conclude that approximately 52 million years ago a transposition of SRY into the ancestral eutherian PAR distal to STS and PRK defined a new PAB in a simian progenitor. By this event, STS and PRK, amongst other genes, were excluded from the X-Y crossover process and thus became susceptible to rearrangements and/or deterioration on the Y chromosome in simian primates.
Subject(s)
Arylsulfatases/genetics , DNA-Binding Proteins/genetics , Evolution, Molecular , Lemur/genetics , Nuclear Proteins , Transcription Factors , X Chromosome/genetics , Y Chromosome/genetics , Animals , Female , Humans , In Situ Hybridization, Fluorescence , Male , Models, Genetic , Phylogeny , Primates/classification , Primates/genetics , Pseudogenes , Sequence Alignment , Sex-Determining Region Y Protein , Species Specificity , Steryl-SulfataseABSTRACT
Cytogenetic analysis, fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) were applied to characterize the Y-chromosomal breakpoints of three XX male patients. Two of these patients show a breakpoint within a protein kinase gene, PRKY, previously described as a hotspot of ectopic recombination between homologous regions on X and Y chromosomes during male meiosis. The slightly different clinical phenotypes of the three patients cannot be correlated with the localization of the breakpoints.
Subject(s)
Turner Syndrome/genetics , Y Chromosome/genetics , Adult , Child , Chorionic Gonadotropin , Cytogenetics , DNA/genetics , Gonadal Steroid Hormones/blood , Humans , In Situ Hybridization, Fluorescence , Infant , Karyotyping , Male , Reverse Transcriptase Polymerase Chain Reaction , Y Chromosome/ultrastructureABSTRACT
To identify genes involved in macrophage development, we used the differential display technique and compared the gene expression profiles for human myeloid HL-60 leukemia cell lines susceptible and resistant to macrophage maturation. We identified a gene coding for a protein kinase, protein kinase X (PRKX), which was expressed in the maturation-susceptible, but not in the resistant, cell line. The expression of the PRKX gene was found to be induced during monocyte, macrophage, and granulocyte maturation of HL-60 cells. We also studied the expression of the PRKX gene in 12 different human tissues and transformed cell lines and found that, among these tissues and cell types, the PRKX gene is expressed only in blood. Among the blood cell lineages, the PRKX gene is specifically expressed in macrophages and granulocytes. Antisense inhibition of PRKX expression blocked terminal development in both the leukemic HL-60 cells and normal peripheral blood monocytes, implying that PRKX is a key mediator of macrophage and granulocyte maturation. Using the HL-60 cell variant deficient in protein kinase C-beta (PKC-beta) and several stable PKC-beta transfectants, we found that PRKX gene expression is under control of PKC-beta; hence PRKX is likely to act downstream of this PKC isozyme in the same signal transduction pathway leading to macrophage maturation.
Subject(s)
Cell Differentiation/physiology , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Enzymologic , Macrophages/cytology , Oligodeoxyribonucleotides, Antisense/pharmacology , Protein Serine-Threonine Kinases/genetics , Calcitriol/pharmacology , Cell Differentiation/drug effects , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic , Genetic Variation , Granulocytes/cytology , Granulocytes/enzymology , HL-60 Cells , Humans , Lymphocytes/cytology , Lymphocytes/enzymology , Macrophage Colony-Stimulating Factor/pharmacology , Macrophages/enzymology , Monocytes/cytology , Monocytes/enzymology , Nuclear Proteins , Oligodeoxyribonucleotides/pharmacology , Organ Specificity , Protein Serine-Threonine Kinases/metabolism , Recombinant Proteins/metabolism , Tetradecanoylphorbol Acetate/pharmacology , Transcription Factors , Transcription, Genetic , TransfectionABSTRACT
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.
Subject(s)
Acetylserotonin O-Methyltransferase/genetics , Evolution, Molecular , Gene Duplication , Methyltransferases/genetics , Pseudogenes , Amino Acid Sequence , Artificial Gene Fusion , Chromosome Mapping/methods , Cloning, Molecular , Humans , Methyltransferases/metabolism , Molecular Sequence Data , Sequence Homology, Amino Acid , Sex Chromosomes , Tissue Distribution , X ChromosomeABSTRACT
XX males and XY females have a sex reversal disorder which can be caused by an abnormal interchange between the X and the Y chromosomes. We have isolated and characterized a novel gene on the Y chromosome, PRKY. This gene is highly homologous to a previously isolated gene from Xp22.3, PRKX, and represents a member of the cAMP-dependent serine threonine protein kinase gene family. Abnormal interchange can occur anywhere on Xp/Yp proximal to SRY. We can show that abnormal interchange happens particularly frequently between PRKX and PRKY. In a collection of 26 XX males and four XY females, between 27 and 35% of the interchanges take place between PRK homologues but at different sites within the gene. PRKY and PRKX are located far from the pseudoautosomal region where XY exchange normally takes place. The unprecedented high sequence identity and identical orientation of PRKY to its homologous partner on the X chromosome, PRKX, explains the high frequency of abnormal pairing and subsequent ectopic recombination, leading to XX males and XY females and to the highest rate of recombination outside the pseudoautosomal region.
Subject(s)
Aneuploidy , Disorders of Sex Development , Gonadal Dysgenesis, 46,XY/genetics , Protein Serine-Threonine Kinases/genetics , X Chromosome , Y Chromosome , Base Sequence , DNA, Complementary , Female , Gonadal Dysgenesis, 46,XY/enzymology , Humans , Male , Molecular Sequence Data , SyndromeABSTRACT
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.
Subject(s)
Arylsulfatases/genetics , Chromosome Mapping , Mitochondrial ADP, ATP Translocases/genetics , Protein Serine-Threonine Kinases/genetics , Receptors, Colony-Stimulating Factor/genetics , Animals , Biological Evolution , Cattle , Cloning, Molecular , Dogs , Female , Gene Library , Humans , In Situ Hybridization, Fluorescence , Male , Protein Kinase C , Sheep , Steryl-Sulfatase , Translocation, Genetic , X Chromosome/genetics , Y ChromosomeABSTRACT
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.
Subject(s)
Body Height/genetics , Chromosome Aberrations , X Chromosome/genetics , Adolescent , Child , Chromosome Breakage , Chromosome Mapping , Female , Humans , In Situ Hybridization, Fluorescence , Sequence DeletionABSTRACT
Several genes located within or proximal to the human PAR in Xp22 have homologues on the Y chromosome and escape, or partly escape, inactivation. To study the evolution of Xp22 genes and their Y homologues, we applied multicolour fluorescence in situ hybridization (FISH) to comparatively map DNA probes for the genes ANT3, XG, ARSD, ARSE (CDPX), PRK, STS, KAL and AMEL to prometaphase chromosomes of the human species and hominoid apes. We demonstrate that the genes residing proximal to the PAR have a highly conserved order on the higher primate X chromosomes but show considerable rearrangements on the Y chromosomes of hominoids. These rearrangements cannot be traced back to a simple model involving only a single or a few evolutionary events. The linear instability of the Y chromosomes gives some insight into the evolutionary isolation of large parts of the Y chromosomes and thus might reflect the isolated evolutionary history of the primate species over millions of years.
Subject(s)
Biological Evolution , Haplorhini/genetics , Hominidae/genetics , X Chromosome/genetics , Y Chromosome/genetics , Animals , Chromosome Mapping , DNA Probes , Genes , Humans , In Situ Hybridization, Fluorescence/methods , Sequence Homology, Nucleic AcidABSTRACT
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.
Subject(s)
Chromosome Deletion , Translocation, Genetic , X Chromosome , Y Chromosome , Abnormalities, Multiple/genetics , Adult , Body Height , Female , Humans , Intellectual Disability/genetics , Karyotyping , ScoliosisABSTRACT
Genes within the differential region of the human Y chromosome do not recombine, and therefore the determination of their location depends on physical mapping. Yeast artificial chromosome (YAC) contigs spanning the euchromatic region of the human Y have become a powerful tool for the generation of an overlapping clone map. With this approach, however, complete physical mapping is difficult in Y euchromatic regions that are rich in repetitive sequences. We have, therefore, made use of the fluorescence in situ hybridization technique as an alternative strategy for physically mapping the PRKY and AMELY genes as well as the TSPY, RBM and DAZ gene families to human Y chromosomes in prometaphase and to extended Y chromatin in interphase. From our results, the following order of gene sequences in interval 3 of the short arm of the human Y chromosome is suggested: TSPY major with few RBM sequences interspersed-PRKY-AMELY-TSPY minor with few RBM sequences interspersed-cen. On the long arm, RBM sequences appear to be distributed over wide regions of intervals 5 and 6 with few TSPY sequences interspersed. Distal to an RBM signal cluster, a large cluster of DAZ signals is located with only a few DAZ and RBM signals overlapping in between the two clusters.
Subject(s)
Chromatin , Chromosome Mapping , In Situ Hybridization, Fluorescence , Transcription Factors , Y Chromosome/genetics , Cell Cycle Proteins , Centromere , Chromatin/genetics , Chromosome Mapping/methods , Chromosomes, Artificial, Yeast , Cosmids , DNA Probes , DNA, Satellite , DNA-Binding Proteins/genetics , Deleted in Azoospermia 1 Protein , Genetic Linkage , Humans , Interphase , Metaphase , Microscopy, Fluorescence , Multigene Family/genetics , Nuclear Proteins/genetics , RNA-Binding Proteins/genetics , Repetitive Sequences, Nucleic Acid , Sex-Determining Region Y ProteinABSTRACT
Recently, we reported the isolation of a new subfamily of serine-threonine protein kinases. This subfamily was shown to consist of at least four members. Sequencing and FISH mapping of all 4 members now reveals that the Y-homolog (PRKY) of the previously mapped PRKX gene (Xp22.3) is located in Yp11.2, in close vicinity to AMELY. The other two copies reside on Xq12-->q13 (PRKXP2) and 15q26 (PRKXP1, containing CA repeat STS D15S87) and represent pseudogenes.
Subject(s)
Chromosomes, Human, Pair 15 , Protein Serine-Threonine Kinases/genetics , Pseudogenes , X Chromosome , Y Chromosome , Base Sequence , Chromosome Mapping , DNA, Complementary , Female , Humans , In Situ Hybridization, Fluorescence , Male , Molecular Sequence DataABSTRACT
We have isolated a gene, PKX1, by virtue of its position within the candidate region for chondrodysplasia punctata in Xp22.3. Although data from one patient render it unlikely that PKX1 is the CDPX gene, this gene shows several interesting features. First, PKX1 appears to encode a novel type of human protein kinase that is related to the catalytic subunit of cAMP-dependent protein kinases and has striking homology to the DC2 protein kinase from Drosophila melanogaster. Second, PKX1 is part of a family of at least four genes or pseudogenes, of which three map to the human sex chromosomes. In contrast to all other genes from the X-specific region of Xp22.3, PKX1 has a homologue on Yp rather than Yq. This is intriguing as it indicates that the single pericentric inversion event hypothesized to have occurred during primate evolution is not sufficient to explain the present X/Y-homology pattern of Xp22.3. Third, we have characterized patients with different chromosomal rearrangements in Xp22.3 or Yp and show that a high proportion of these have occurred within the PKX1 locus. This suggests that the PKX1 gene, besides harbouring a previously described hot-spot for illegitimate Xp/Yp-recombination, contains additional sequences predisposing to chromosomal breakage events.
Subject(s)
Protein Kinases/genetics , X Chromosome , Amino Acid Sequence , Animals , Base Sequence , Biological Evolution , Chromosome Mapping , Cloning, Molecular , DNA, Complementary/genetics , Drosophila melanogaster/genetics , Female , Gene Expression , Gene Rearrangement , Humans , Male , Molecular Sequence Data , Multigene Family , Recombination, Genetic , Sequence Homology, Amino Acid , Y ChromosomeABSTRACT
Comparative in situ hybridization in various primate species has revealed a pseudoautosomal location for the human ANT3 gene and an X-specific location for the steroid sulfatase (STS) gene throughout the higher primate species up to the New World monkeys. However, ANT3 and STS map together on an autosome of two prosimian species of the genus Lemur and Eulemur. These results suggest an autosome-to-X/Y translocation after the simians radiated from the prosimians, resulting in a pseudoautosomal location of genes such as ANT3 and STS. In simian primates, STS then became X-specific by a pericentric inversion in the Y chromosome followed by mutational inactivation of the Y allele.