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.

62 The species and chromosomal distribution of the centromeric -satellite I sequence from sheep in the tribe Caprini and other Bovidae Chaves R, Guedes-Pinto H, Heslop-Harrison JS, Schwarzacher T 67 TSPY variants in six loci on the human Y chromosome Dechend F, Williams G, Skawran B, Schubert S, Krawczak M, Tyler-Smith C, Schmidtke J 72 Local mechanisms in sex specific morphogenesis Drews U 81 Microdeletion 4p16.3 in three unrelated patients with Wolf-Hirschhorn syndrome Dufke A, Seidel J, Schöning M, Döbler-Neumann M, Kelbova C, Liehr T, Beensen V, Backsch C, Klein-Vogler U, Enders H 85 A second case of inv(4)pat with both recombinants in the offspring: rec dup(4q) in a girl with Wolf-Hirschhorn syndrome and rec dup(4p) Dufke A, Eggermann K, Balg S, Stengel-Rutkowski S, Enders H, Kaiser P

DNA sequencing reveals that the genomes of the human, gorilla and chimpanzee share more than 98% homology. Comparative chromosome painting and gene mapping have demonstrated that only a few rearrangements of a putative ancestral mammalian genome occurred during great ape and human evolution. However, interspecies representational difference analysis (RDA) of the gorilla between human and gorilla revealed gorilla-specific DNA sequences. Cloning and sequencing of gorilla-specific DNA sequences indicate that there are repetitive elements. Gorilla-specific DNA sequences were mapped by fluorescence in-situ hybridization (FISH) to the subcentromeric/centromeric regions of three pairs of gorilla submetacentric chromosomes. These sequences could represent either ancient sequences that got lost in other species, such as human and orang-utan, or, more likely, recent sequences which evolved or originated specifically in the gorilla genome.

We report on a newborn female patient with a de novo pure partial duplication of 7q. The clinical features are compared with those of 19 cases from the literature with pure partial duplication of different segments of 7q. Conventional cytogenetic investigation led to the diagnosis of duplication of bands q21.3 to q35. This was confirmed by chromosome painting and by fluorescence in situ hybridization with different YAC probes from the duplicated region.

Comparative genome analysis between two distantly related species allows the organization of genes to be traced from a common ancestor. When several genes are mapped in one species and these genes are then localized in the distantly related species, then the genomic content of this region can be inferred in the common ancestor. If two species are closely related in evolutionary terms, then larger blocks of the genome will be conserved. Therefore these segments can be easily traced back to a common ancestor. Such comparisons have made it possible to trace the evolutionary origins of regions of the mammalian X chromosome (1).

impala) 62 lervia (aoudad) 62 Aotus trivirgatus (New World monkey) 113 Bos taurus (bovine) 62, 113 Canis familiaris (dog) 113 Capra hircus (goat) 62 Capreolus capreolus (roe) 113 Connochaetes taurinus (gnu) 62 Equus caballus (horse) 113 Hippotragus niger (sable antelope) 62 Kobus ellipsiprymnus, K. kob, K. leche, K. megaceros (antelope) 128 Macaca fascicularis (Old World monkey) 113

The mammalian X and Y chromosomes are very different in size and gene content. The Y chromosome is much smaller than the X and consists largely of highly repeated non-coding DNA, containing few active genes. The 65-Mb human Y is homologous to the X over two small pseudoautosomal regions which together contain 13 active genes. The heterochromatic distal half of the human Yq is entirely composed of highly repeated non-coding DNA, and even the euchromatic portion of the differential region is largely composed of non-coding repeated sequences, amongst which about 30 active genes are located. The basic marsupial Y chromosome (about 10 Mb) is much smaller than that of humans or other eutherian mammals. It appears to include no PAR, since it does not undergo homologous pairing, synaptonemal complex formation or recombination with the X. We show here that the tiny dunnart Y chromosome does not share cytogenetically detectable sequences with any other chromosome, suggesting that it contains many fewer repetitive DNA sequences than the human or mouse Y chromosomes. However, it shares several genes with the human and/or mouse Y chromosome, including the sex determining gene SRY and the candidate spermatogenesis gene RBMY, implying that the marsupial and eutherian Y are monophyletic. This minimal mammalian Y chromosome might provide a good model Y in which to hunt for new mammalian Y specific genes.

A 2n = 14 karyotype is shared by some species in each of the marsupial orders in Australian and American superfamilies, suggesting that the ancestral marsupial chromosome complement was 2n = 14. We have used chromosome painting between distantly related marsupial species to discover whether genome arrangements in 2n = 14 species in two Australian orders support this hypothesis. Cross-species chromosome painting was used to investigate chromosome rearrangements between a macropodid species Macropus eugenii (2n = 16) and a wombat species in a different suborder (Lasiorhinus latifrons, 2n = 14), and a dasyurid species in a different order (Sminthopsis macroura, 2n = 14). We demonstrate that many chromosome regions are conserved between all three species, and deduce how the similar 2n = 14 karyotypes of species in the two orders are related to a common ancestral 2n = 14 karyotype.

Marsupial mammals show extraordinary karyotype stability, with 2n = 14 considered ancestral. However, macropodid marsupials (kangaroos and wallabies) exhibit a considerable variety of karyotypes, with a hypothesised ancestral karyotype of 2n = 22. Speciation and karyotypic diversity in rock wallabies (Petrogale) is exceptional. We used cross species chromosome painting to examine the chromosome evolution between the tammar wallaby (2n = 16) and three 2n = 22 rock wallaby species groups with the putative ancestral karyotype. Hybridization of chromosome paints prepared from flow sorted chromosomes of the tammar wallaby to Petrogale spp., showed that this ancestral karyotype is largely conserved among 2n = 22 rock wallaby species, and confirmed the identity of ancestral chromosomes which fused to produce the bi-armed chromosomes of the 2n = 16 tammar wallaby. These results illustrate the fission-fusion process of karyotype evolution characteristic of the kangaroo group.

Thylogale spp. (pademelons) retain the plesiomorphic (ancestral) 2n = 22 karyotype for the marsupial family Macropodidae (kangaroos and wallabies). The swamp wallaby, Wallabia bicolor, has the most derived macropodid karyotype with the lowest chromosome number (2n = 10 female, 11 male), and a multiple sex chromosome system (XX female, XY1Y2 male). All but one of the W. bicolor chromosomes are fusion chromosomes. Two of these chromosomes, the X chromosome and chromosome 1, are composed of three plesiomorphic Thylogale-like chromosomes. The distribution of the vertebrate telomeric sequence (T2AG3)n was examined by fluorescence in situ hybridization (FISH) in both species and a 'map' of non-telomeric (T2AG3)n sites on W. bicolor chromosomes relative to Thylogale chromosomes was constructed. (T2AG3)n signals were observed at six fusion sites in the four fusions chromosomes examined, indicating that the (T2AG3)n sequence is consistently retained during fusions. The distribution of the interstitial signals on the long arm of chromosome 1 of W. bicolor and the X chromosome suggests how a combination of inversions, fusions and centromeric transpositions have resulted in interstitial telomeric sequence.

Ohno’s early suggestions about the origin of sex chromosomes and the consequences of alterations of dosage of X and Y genes have provided an important framework for understanding sex chromosome organization, function and evolution. Here we review evidence that heteromorphic sex chromosomes evolved from an autosomal pair, and that one of the consequences of X–Y differentiation is the evolution of dosage compensation by X inactivation and upregulation of the active X, which in turn, has selected for a highly conserved X chromosome.

Comparative chromosome G-/R-banding, comparative gene mapping and chromosome painting techniques have demonstrated that only few chromosomal rearrangements occurred during great ape and human evolution. Interspecies comparative genome hybridization (CGH), used here in this study, between human, gorilla and pygmy chimpanzee revealed species-specific regions in all three species. In contrast to the human, a far more complex distribution of species-specific blocks was detected with CGH in gorilla and pygmy chimpanzee. Most of these blocks coincide with already described heterochromatic regions on gorilla and chimpanzee chromosomes. Representational difference analysis (RDA) was used to subtract the complex genome of gorilla against human in order to enrich gorilla-specific DNA sequences. Gorilla-specific clones isolated with this technique revealed a 32-bp repeat unit. These clones were mapped by fluorescence in situ hybridization (FISH) to the telomeric regions of gorilla chromosomes that had been shown by interspecies CGH to contain species-specific sequences.

The human X and Y chromosomes share two homologous pseudoautosomal regions (PARs) which pair and recombine at meiosis. PAR1 lies at the tips of the short arms, and the smaller PAR2 at the tips of the long arms. PAR1 contains several active genes, and has been thought to be critical for pairing and fertility. The inconsistent gene content of the PARs between different species of eutherian ('placental') mammals suggests that gene content is immaterial to function, and the failure to detect a PAR at all in some rodents and all marsupials implies that homologous pairing is not universally essential for fertility. The autosomal localization of marsupial homologues of human PAR1 genes and their co-localization with human Xp22 genes implies that the human PAR1 represents a relic of part of an autosomal region added to both X and Y chromosomes between 80 and 130 MYrBP. The same argument may be made for part of PAR2. Independent additions to the sex chromosomes of macropodid marsupials and monotremes can also be inferred from comparative mapping. We conclude that the PARs are relics of differential additions, loss, rearrangement and degradation of the Y chromosome in different mammalian lineages.