RESUMO
In type I blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), eyelid abnormalities are associated with ovarian failure. Type II BPES shows only the eyelid defects, but both types map to chromosome 3q23. We have positionally cloned a novel, putative winged helix/forkhead transcription factor gene, FOXL2, that is mutated to produce truncated proteins in type I families and larger proteins in type II. Consistent with an involvement in those tissues, FOXL2 is selectively expressed in the mesenchyme of developing mouse eyelids and in adult ovarian follicles; in adult humans, it appears predominantly in the ovary. FOXL2 represents a candidate gene for the polled/intersex syndrome XX sex-reversal goat.
Assuntos
Anormalidades Múltiplas/genética , Doenças Palpebrais/genética , Mutação , Doenças Nasais/genética , Adulto , Sequência de Aminoácidos , Animais , Sequência de Bases , Blefarofimose/genética , Blefaroptose/genética , Criança , Segregação de Cromossomos , Cromossomos Humanos Par 3 , Códon sem Sentido , Proteínas de Ligação a DNA/genética , Pálpebras/embriologia , Feminino , Proteína Forkhead Box L2 , Fatores de Transcrição Forkhead , Duplicação Gênica , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Ovário/embriologia , Linhagem , ATPases Translocadoras de Prótons , Homologia de Sequência de Aminoácidos , Síndrome , Fatores de Transcrição/genéticaRESUMO
The generation of panels of somatic cell hybrids specific for chimpanzee, gorilla, orangutan, and olive baboon is reported. The chromosome content of each hybrid clone was characterized using reverse painting on human normal metaphases and by the use of appropriate sequence tag sites (STSs), one for each chromosome arm. These resources can be advantageously exploited in the characterization of chromosome architecture of different primate species, with special reference to the discrimination of inter- and intra-chromosomal arrangement of segmental duplications.
Assuntos
Hominidae/genética , Células Híbridas/química , Células Híbridas/metabolismo , Papio hamadryas/genética , Animais , Células CHO/química , Células CHO/metabolismo , Linhagem Celular , Cromossomos de Mamíferos/genética , Cricetinae , Cricetulus/genética , Gorilla gorilla/genética , Humanos , Pan troglodytes/genética , Pongo pygmaeus/genética , Sitios de Sequências RotuladasRESUMO
We have generated a panel of 20 somatic cell hybrids retaining fragments of human chromosome 12. Each hybrid was characterized cytogenetically by reverse fluorescence in situ hybridization (FISH) and molecularly by 24 sequence tagged sites (STSs) spaced evenly along the chromosome. The panel can be exploited to map subregionally DNA sequences on chromosome 12 and to generate partial chromosome paints useful in the characterization of chromosomal rearrangements involving this chromosome. Furthermore, a panel of 58 yeast artificial chromosomes (YACs) mapping to chromosome 12 was characterized by FISH experiments on normal human metaphases. A subset of this panel is recognized by the STSs used in the somatic cell hybrid characterization. In this way a correlation between the genetic and the physical maps of this chromosome can be established.
Assuntos
Cromossomos Humanos Par 12/genética , Análise Citogenética , Animais , Mapeamento Cromossômico , Cromossomos Artificiais de Levedura , Cricetinae , Humanos , Células Híbridas , Hibridização in Situ Fluorescente , Sitios de Sequências RotuladasAssuntos
Coloração Cromossômica/métodos , Animais , Sequência de Bases , Cromossomos Humanos/genética , Cricetinae , Primers do DNA/genética , Humanos , Células Híbridas , Hibridização in Situ Fluorescente , Marcação In Situ das Extremidades Cortadas , Microscopia de Fluorescência , Reação em Cadeia da Polimerase/métodosRESUMO
BACKGROUND: In order to clarify the relationship between chromosomal rearrangements, sperm morphology and interchromosomal effects (ICE), we studied the spermatogenetic defects in seven infertile Robertsonian translocation carriers. METHODS: Lymphocyte karyotypes were evaluated using Giemsa-Trypsin-Giemsa banding and fluorescence in-situ hybridization (FISH). Semen analysis was performed by light and transmission electron microscopy. FISH of sperm nuclei was carried out to detect possible ICE. RESULTS: Lymphocyte karyotype analysis revealed five t(13;14), one t(13;21) and one t(14;22) carriers. Sperm ultrastructural examination highlighted a higher percentage of immaturity, apoptosis and necrosis than in controls. Aneuploidies of gonosomes were detected in sperm from five out of six carriers of Robertsonian translocation, whereas aneuploidy of chromosome 18 was evident in three out of six carriers. The frequencies of diploidy were altered in all cases. CONCLUSIONS: Since these infertile patients showed severe spermatogenetic impairment from the morphological and meiotic points of view, we recommend detailed sperm ultrastructural and chromosomal analysis before undertaking ICSI cycles in Robertsonian translocation carriers.
Assuntos
Aneuploidia , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Espermatozoides/patologia , Translocação Genética , Adulto , Cromossomos Humanos Par 18 , Cromossomos Humanos X , Cromossomos Humanos Y , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Espermatozoides/ultraestruturaRESUMO
We present the first documented NOR suppression in a hybridoma other than man-mouse for the hamster-chimpanzee hybrid cell line R48-26. Alu PCR and chromosome painting showed that in this cell line chimpanzee chromosomes 13-15-23 are maintained. NORs on chimpanzee chromosomes 15-23, whose presence was directly verified by FISH with H 28s rDNA, resulted inactive while telomeric rDNA on hamster chromosomes resulted active even if hamster chromosomes presented extensive rearrangements. We observed an all or nothing model in accordance with a model of regulation by selective transcriptional factors. The rearrangements of hamster chromosomes have not involved the location of NORs because they maintain a telomeric position.
Assuntos
Cricetulus/genética , Regulação Neoplásica da Expressão Gênica/genética , Região Organizadora do Nucléolo/genética , Pan troglodytes/genética , Animais , Células CHO , Linhagem Celular , Coloração Cromossômica , Cricetinae , DNA Ribossômico/genética , Células Híbridas/metabolismo , Hibridização in Situ Fluorescente , RNA Ribossômico 28S/genética , Telômero/genética , Células Tumorais CultivadasRESUMO
A panel of chimpanzee-human somatic cell hybrids was characterized by dual Alu-PCR of the chimpanzee DNA in the hybrid and subsequent hybridization of the labeled PCR products to human and chimpanzee chromosomes. In addition to the identification of the intact chimpanzee chromosomes retained in each hybrid, chromosome fragments were identified that will be useful in regional mapping. This technique also revealed the presence of centric inversions.
Assuntos
Células Híbridas , Animais , Sequência de Bases , Células CHO , Cromossomos , Cricetinae , Cricetulus , Primers do DNA , Humanos , Células Híbridas/ultraestrutura , Dados de Sequência Molecular , Pan troglodytes , Reação em Cadeia da PolimeraseRESUMO
Twenty-seven human alphoid DNA probes have been hybridized in situ to metaphase spreads of the common chimpanzee (PTR), the pigmy chimpanzee (PPA), and the gorilla (GGO) to investigate the evolutionary relationship between the centromeric regions of the great ape chromosomes. The surprising results showed that the vast majority of the probes did not recognize their corresponding homologous chromosomes. Alphoid sequences belonging to the suprachromosomal family 1 (chromosomes 1, 3, 5, 6, 7, 10, 12, 16, and 19) yielded very heterogeneous results: some probes gave intense signals, but always on nonhomologous chromosomes; others did not produce any hybridization signal. Almost all probes belonging to the suprachromosomal family 2 (chromosomes 2, 4, 8, 9, 13, 14, 15, 18, 20, 21, and 22) recognized a single chromosome: chromosome 11 (phylogenetic IX) in PTR and PPA and chromosome 19 (phylogenetic V) in GGO. Localization of probes of suprachromosomal family 3 (chromosomes 1, 11, 17, and X) was found to be substantially conserved in PTR and PPA, but not in GGO. Probe pDMX1, specific for the human X chromosome, was the only sequence detecting its corresponding chromosome in all three species. PPA chromosomes I, IIp, IIq, IV, V, VI, and XVIII were never labeled, even under low-stringency hybridization conditions, by the 27 alphoid probes used in this study. These results, with particular reference to differences found in the two related species PTR and PPA, suggest that alphoid centromeric sequences underwent a very rapid evolution.
Assuntos
Centrômero/genética , DNA Satélite/genética , Hominidae/genética , Filogenia , Sequências Repetitivas de Ácido Nucleico , Animais , Linhagem Celular , Mapeamento Cromossômico , Gorilla gorilla/genética , Humanos , Processamento de Imagem Assistida por Computador , Hibridização in Situ Fluorescente , Masculino , Pan troglodytes/genética , Especificidade da EspécieRESUMO
DNA samples from about 100 human-hamster somatic cell hybrids, previously characterized by conventional banding techniques, were amplified with dual-Alu PCR. The products were then used as probes in FISH experiments on normal human metaphases for an accurate cytogenetic characterization of the human material retained in each hybrid. In addition to entire chromosomes, most hybrids were found to contain one or a few chromosome fragments, as a result of rearrangements that had occurred in vitro. Forty additional primary hybrids, in which conventional cytogenetic analysis failed to reveal any complete human chromosome, contained many human chromosome fragments. More than 300 chromosome fragments were scored and their precise chromosomal location recorded. We show data indicating that subchromosomal painting libraries generated from these hybrids can be favorably used in the fine characterization of chromosomal rearrangements encountered in clinical cytogenetics or in tumor cytogenetics, and in tracking chromosomal changes that occurred in primate evolution.
Assuntos
Cromossomos Humanos , Genoma Humano , Animais , Sequência de Bases , Mapeamento Cromossômico , Cricetinae , Primers do DNA , Biblioteca Gênica , Humanos , Células Híbridas , Hibridização in Situ Fluorescente/métodos , Cariotipagem , Linfócitos/citologia , Metáfase , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Sequências Repetitivas de Ácido NucleicoRESUMO
We have isolated and characterized two human alphoid DNA clones: p4n1/4 and pZ4.1. Clone p4n1/4 identifies specifically the centromeric region of chromosome 4; pZ4.1 recognizes a subset of alphoid DNA shared by chromosomes 4 and 9. The specificity was determined using fluorescence in situ hybridization experiments on metaphase spreads and Southern blotting analysis of human-hamster somatic cell hybrids. The genomic organization of both subsets was also investigated. Comparative mapping on chimpanzee and gorilla chromosomes was performed. p4n1/4 hybridizes to chimpanzee chromosomes 11 and 13, homologs of human chromosomes 9 and 2q, respectively. On gorilla metaphase spreads, p4n1/4 hybridizes exclusively to the centromeric region of chromosome 19, partially homologous to human chromosome 17. No hybridization signal was detected on chromosome 3 of both chimpanzee and gorilla, in both species homolog of human chromosome 4. Identical comparative mapping results were obtained using pZ4.1 probe, although the latter recognizes an alphoid subset distinct from the one recognized by p4n1/4. The implications of these results in the evolution of centromeric regions of primate chromosomes are discussed.
Assuntos
Cromossomos Humanos Par 4 , DNA Satélite/genética , Animais , Southern Blotting , Células CHO , Linhagem Celular , Mapeamento Cromossômico , Cromossomos Humanos Par 9 , Clonagem Molecular , Cricetinae , DNA , Gorilla gorilla , Humanos , Células Híbridas , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Pan troglodytes , Pongo pygmaeus , Homologia de Sequência do Ácido NucleicoRESUMO
FISH experiments on metaphase chromosomes, interphase nuclei, and extended chromatin were performed to investigate the structural organization of alphoid subsets coexisting on human chromosomes 1, 4, 5, 7, 9, 15, 18, and 19. Results indicate that multiple subsets present on chromosomes 5, 7, 15, 18, and 19 are organized in structurally distinct and contiguous domains, while those on chromosomes 4 and 9 give perfectly overlapping signals. Chromosome 1 shows a peculiar organization: probe pAL1, specific for this chromosome, detects two distinct domains separated by the subset identified by probe pZ5.1. The order along the chromosome of alphoid subsets lying on chromosomes 5, 7, 15, 18, and 19, organized in distinct blocks, has also been established. The relationship between the structural organization of these alphoid sequences and their evolutionary history in great apes is discussed.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos/genética , DNA Satélite/genética , Animais , Cromatina/ultraestrutura , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 4/genética , Cromossomos Humanos Par 5/genética , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 9/genética , Sondas de DNA , Gorilla gorilla/genética , Humanos , Hibridização In Situ , Interfase , Metáfase , Pan troglodytes/genéticaRESUMO
We have investigated, by fluorescence in situ hybridization (FISH), the cytogenetic evolution of the Y chromosome in primates using 17 yeast artificial chromosomes, representative of the Y-specific euchromatic region of the human chromosome Y. The FISH experiments were performed on great apes (Homo sapiens, Pan troglodytes, Gorilla gorilla and Pongo pygmaeus pygmaeus), and on two Old World monkeys species as an outgroup (Cercopitecidae Macaca fascicularis and Papio anubis). The results showed that this peculiar chromosome has undergone rapid and unconstrained evolution both in sequence content and organization.
Assuntos
Evolução Molecular , Primatas/genética , Cromossomo Y/genética , Animais , Cercopithecidae/genética , Cromossomos Artificiais de Levedura , Mecanismo Genético de Compensação de Dose , Gorilla gorilla/genética , Humanos , Hibridização in Situ Fluorescente , Macaca fascicularis/genética , Pan troglodytes/genética , Papio/genética , Pongo pygmaeus/genética , Pseudogenes , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Cromossomo X/genéticaRESUMO
BACKGROUND: Peculiar sperm defects are described in a sterile man heterozygous for a balanced translocation t(10;15) (q26;q12). As this structural reorganization was absent in the parents, the translocation must have appeared de novo in the present patient. METHODS: Spermatozoa were analysed under light and transmission electron microscopy (TEM). Fluorescence in-situ hybridization (FISH) was performed on the lymphocyte karyotype. Aneuploidy frequencies of chromosomes 18, X and Y in sperm nuclei, not involved in the translocation, were investigated using three-colour FISH. Dual- colour FISH was used to evaluate segregation of chromosomes 10, 15 in decondensed sperm nuclei. Moreover, three-colour FISH, using telomeric probes for chromosomes 10, 15 was performed in order to distinguish balanced and unbalanced gametes. RESULTS AND CONCLUSIONS: Overall, structural characteristics indicate general immaturity of the germinal cells. FISH sperm analysis detected an increase in chromosome 18 disomy (0.81%) suggesting an interchromosomal effect. A high frequency of diploidies, particularly 18,18,X,X and 18,18,X,Y, was also found. FISH segregation analysis for chromosomes 10, 15 indicated that 32.8% were balanced gametes, whereas 68.2% were unbalanced. Taken together, these data demonstrate in a male carrier of a reciprocal translocation t(10;15) the presence of diffuse ultrastructural sperm alterations and a high frequency of sperm aneuploidies. The existence of a correlation among these factors is proposed.
Assuntos
Cromossomos Humanos Par 15/genética , Infertilidade Masculina/genética , Espermatozoides/ultraestrutura , Translocação Genética , Adulto , Aneuploidia , Estudos de Casos e Controles , Senescência Celular , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 18/genética , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Diploide , Frequência do Gene , Heterozigoto , Humanos , Hibridização in Situ Fluorescente , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Cariotipagem , Masculino , Microscopia EletrônicaRESUMO
We report the characterization, by reverse fluorescence in situ hybridization (FISH), of 59 hybrids retaining fragments of human chromosome 5. Most of these hybrids are radiation hybrids generated by gamma irradiating, at low dosage, a monochromosomal hybrid retaining chromosome 5 as its only human contribution. The partial chromosome paints generated from these hybrids will make powerful tools for cytogenetic investigations, especially on the cytogenetic evolution of primates, and examples are reported. The molecular characterization of these hybrids was refined using 74 sequence-tagged sites (STSs), which allowed the physical dissection of chromosome 5 into 71 distinct regions with an average length of 2.7 Mb. The panel, therefore, is also suitable for high-precision subregional mapping of new genes or sequences located on chromosome 5. As an additional resource for cytogenetic studies involving chromosome 5, we report the characterization, by FISH, of 73 YACs from CEPH. The vast majority of these YACs are recognized by at least one of the STSs used for hybrid characterization, thus enabling the integrated use of YACs and partial chromosome paints derived from the hybrids.
Assuntos
Cromossomos Artificiais de Levedura/genética , Cromossomos Humanos Par 5/genética , Células Híbridas , Animais , Mapeamento Cromossômico , Cromossomos Humanos Par 5/ultraestrutura , Cromossomos Humanos Par 8/genética , Cromossomos Humanos Par 8/ultraestrutura , Clonagem Molecular , Cricetinae , Feminino , Humanos , Hibridização in Situ Fluorescente , Pan troglodytes/genética , Sitios de Sequências Rotuladas , Translocação GenéticaRESUMO
We have used Alu polymerase chain reaction generated probes from rearranged human/rodent somatic cell hybrids for fluorescence in situ hybridization and comparative mapping of some intrachromosomal changes in the karyotypes of great apes (Pan troglodytes, P. paniscus, Gorilla gorilla, Pongo pygmaeus), a gibbon (Hylobates lar), and an Old World monkey (Macaca fuscata). Probes containing chromosomes 2 and 18 fragments confirmed inversions already suggested by the banding pattern of great ape homologues. However, a chromosome 3 fragment showed complex rearrangements in the gibbon and macaque karyotype which were previously not well defined from banding. 'Subchromosomal painting' will allow the identification of intrachromosomal changes on the basis of DNA homology and provides a powerful method to study karyological and genomic evolution.
Assuntos
Mapeamento Cromossômico/métodos , Hominidae/genética , Células Híbridas/química , Hylobates/genética , Hibridização in Situ Fluorescente , Macaca/genética , Animais , Evolução Biológica , Bandeamento Cromossômico , Cromossomos Humanos Par 18/química , Cromossomos Humanos Par 2/química , Sondas de DNA , Rearranjo Gênico , Humanos , Cariotipagem , Camundongos , Filogenia , Reação em Cadeia da Polimerase , Ratos , Sequências Repetitivas de Ácido NucleicoRESUMO
UNLABELLED: Hereditary neuropathy with liability to pressure palsies (HNPP) and hereditary motor-sensory neuropathy type IA (HMSN IA) are quite distinct clinical entities recently associated to deletion and duplication, respectively, of the 17p11.2 segment including the gene for peripheral myelin protein 22 (PMP-22). We studied the electrophysiological features of 48 HNPP and 62 HMSN IA motor nerves. Conduction velocities (CV) and compound muscle action potential amplitudes were significantly reduced and distal latencies prolonged in HMSN IA compared to HNPP. CV was uniformly slowed in HMSN IA nerves whereas in HNPP it was focally slowed in 80% of ulnar and 12% of peroneal nerves at usual compression sites. Conduction block was present in 6% of HNPP nerves but in none of HMSN IA. IN CONCLUSION: (1) HMSN IA with 17p11.2 duplication presents marked, diffuse, and uniform slowing; (2) HNPP with 17p11.2 deletion presents focal electrophysiological abnormalities possibly correlated with the presence of tomaculae; and (3) under- and overexpression of PMP-22 in concurrence with environmental factors might be responsible for the distinctive features of HNPP and HMSN IA.
Assuntos
Aberrações Cromossômicas , Deleção Cromossômica , Transtornos Cromossômicos , Neuropatia Hereditária Motora e Sensorial/genética , Doenças do Sistema Nervoso Periférico/genética , Potenciais de Ação , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/inervação , Músculos/fisiopatologia , Condução Nervosa , Paralisia/genética , Paralisia/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , PressãoRESUMO
The demyelinating type of hereditary motor and sensory neuropathy (HMSN I) is characterized by progressive weakness and atrophy of leg muscles. Six patients (age, 25-79 yr) belonging to three generations had calf hypertrophy (6 of 6), foot drop or difficulty with heel walking (4 of 6), pes cavus (3 of 6), absent or depressed tendon jerks in the lower limbs (4 of 6), and mild distal sensory loss (3 of 6). No other family member had leg atrophy. Motor conduction velocities ranged from 20 to 40 m/sec. Sural nerve biopsy showed loss of large myelinated fibers, numerous onion bulbs, and segmental demyelination and remyelination. Computed tomographic scans of leg muscles and histological and morphometric findings in gastrocnemius revealed true muscular hypertrophy. Southern blot and fluorescence in situ hybridization documented the duplication of the entire 17p11.2 segment associated with classical HMSN IA. The pathogenesis of muscle hypertrophy in our cases is unclear. Chronic leg muscle weakness and long-standing partial denervation might cause calf enlargement by a combination of compensatory "work-induced" and "stretch-induced" fiber hypertrophy. Alternatively, that all the affected family members presented calf hypertrophy might suggest the action of a genetic factor associated with the duplication at 17p11.2.
Assuntos
Cromossomos Humanos Par 17 , Neuropatia Hereditária Motora e Sensorial/genética , Família Multigênica/genética , Músculos/patologia , Adulto , Idoso , Biópsia , Eletromiografia , Feminino , Neuropatia Hereditária Motora e Sensorial/patologia , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Humanos , Hipertrofia/genética , Perna (Membro)/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Músculos/diagnóstico por imagem , Condução Nervosa/fisiologia , Linhagem , Tomografia Computadorizada por Raios XRESUMO
Differential screening of a cDNA library constructed from human umbilical vein endothelial cells exposed for 1 h to interleukin-1 beta (IL-1 beta) has led to the identification of a novel gene (PTX3) related to pentaxins (C-reactive protein and serum amyloid P component in man), a subclass of acute phase proteins. Sequencing of the full-length cDNA clone and RNase mapping revealed that the PTX3 transcript is 1861 base pairs long and has a unique transcription start site. The predicted protein sequence of 381 amino acids is highly similar to pentaxins in its COOH-terminal half where it also contains a typical 8-amino acid "pentaxin signature" sequence. The NH2-terminal half of PTX3 shows no similarity to any known protein sequence and initiates with a putative signal peptide indicating that PTX3 is secreted. The genome of PTX3 is organized into three exons. Interestingly, the region of homology between PTX3 and pentaxins corresponds to the third PTX3 exon. The PTX3 gene has been localized on human chromosome 3 band q25 by Southern blots of somatic cell hybrids and by in situ hybridization. The PTX3 mRNA is induced in endothelial, hepatic, and fibroblastic cells by IL-1 beta and tumor necrosis factor alpha but not by IL-6 and interferon-gamma. PTX3 may represent a novel marker of inflammatory reactions, particularly those involving the vessel wall.
Assuntos
Endotélio Vascular/fisiologia , Genes , Interleucina-1/farmacologia , Componente Amiloide P Sérico/genética , Sequência de Aminoácidos , Sequência de Bases , Proteína C-Reativa/genética , Cromossomos Humanos Par 3 , Clonagem Molecular , Citocinas/farmacologia , DNA/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Dados de Sequência Molecular , RNA Mensageiro/genética , Alinhamento de SequênciaRESUMO
We have generated a panel of 55 somatic cell hybrids retaining fragments of human chromosome 4. Each hybrid has been characterized cytogenetically by FISH and molecularly by 37 STSs, evenly spaced along the chromosome. The panel can be exploited to map subregionally DNA sequences on chromosome 4 and to generate partial chromosome paints useful in the characterization of chromosomal rearrangements involving this chromosome. Furthermore, a panel of 84 YACs mapping on chromosome 4 has been characterized by FISH. A subset of this panel is recognized by STSs used in the somatic cell hybrid characterization. In this way a correlation between the genetic and the physical maps can be established. These resources have been used to investigate the conservation of the phylogenetic chromosome IV in great apes. The results indicate that all the pericentric inversions that differentiate chromosome IV in these species are distinct and that one of the breakpoints frequently lies very close to the centromere. In 4 instances, the YAC containing the breakpoint was identified. The breakpoint in IVq of PTR and MMU lies in the same YAC, suggesting that this breakpoint has been utilized twice in the evolutionary history of this chromosome.