Human cytogenetics at Johns Hopkins Hospital, 1959–1962

Abstract: An account is given of the introduction of human cytogenetics to the Division of Medical Genetics at Johns Hopkins Hospital, and the first 3 years' work of the chromosome diagnostic laboratory that was established at the time. Research on human sex chromosome disorders, including novel discoveries in the Turner and Klinefelter syndromes, is described together with original observations on chromosome behavior at mitosis. It is written in celebration of the centenary of the birth of Victor McKusick, the acknowledged father of Medical Genetics, who established the Division and had the foresight to ensure that it included the investigation of human chromosomes

Human cytogenetics at Johns Hopkins Hospital, 1959–1962

Abstract: An account is given of the introduction of human cytogenetics to the Division of Medical Genetics at Johns Hopkins Hospital, and the first 3 years' work of the chromosome diagnostic laboratory that was established at the time. Research on human sex chromosome disorders, including novel discoveries in the Turner and Klinefelter syndromes, is described together with original observations on chromosome behavior at mitosis. It is written in celebration of the centenary of the birth of Victor McKusick, the acknowledged father of Medical Genetics, who established the Division and had the foresight to ensure that it included the investigation of human chromosomes

Afrotheria genome; overestimation of genome size and distinct chromosome GC content revealed by flow karyotyping

AbstractAfrotheria genome size is reported to be over 50% larger than that of human, but we show that this is a gross overestimate. Although genome sequencing in Afrotheria is not complete, extensive homology with human has been revealed by chromosome painting. We provide new data on chromosome size and GC content in four Afrotherian species using flow karyotyping. Genome sizes are 4.13Gb in aardvark, 4.01Gb in African elephant, 3.69Gb in golden mole and 3.31Gb in manatee, whereas published results show a mean of 5.18Gb for Afrotheria. Genome GC content shows a negative correlation with size, indicating that this is due to differences in the amount of AT-rich sequences. Low genome GC content and small variance in chromosome GC content are characteristic of aardvark and elephant and may be associated with the high degree of conserved synteny, suggesting that these are features of the Afrotherian ancestral genome

Chromhome: a rich internet application for accessing comparative chromosome homology maps.

BACKGROUND: Comparative genomics has become a significant research area in recent years, following the availability of a number of sequenced genomes. The comparison of genomes is of great importance in the analysis of functionally important genome regions. It can also be used to understand the phylogenetic relationships of species and the mechanisms leading to rearrangement of karyotypes during evolution. Many species have been studied at the cytogenetic level by cross species chromosome painting. With the large amount of such information, it has become vital to computerize the data and make them accessible worldwide. Chromhome http://www.chromhome.org is a comprehensive web application that is designed to provide cytogenetic comparisons among species and to fulfil this need. RESULTS: The Chromhome application architecture is multi-tiered with an interactive client layer, business logic and database layers. Enterprise java platform with open source framework OpenLaszlo is used to implement the Rich Internet Chromhome Application. Cross species comparative mapping raw data are collected and the processed information is stored into MySQL Chromhome database. Chromhome Release 1.0 contains 109 homology maps from 51 species. The data cover species from 14 orders and 30 families. The homology map displays all the chromosomes of the compared species as one image, making comparisons among species easier. Inferred data also provides maps of homologous regions that could serve as a guideline for researchers involved in phylogenetic or evolution based studies. CONCLUSION: Chromhome provides a useful resource for comparative genomics, holding graphical homology maps of a wide range of species. It brings together cytogenetic data of many genomes under one roof. Inferred painting can often determine the chromosomal homologous regions between two species, if each has been compared with a common third species. Inferred painting greatly reduces the need to map entire genomes and helps focus only on relevant regions of the chromosomes of the species under study. Future releases of Chromhome will accommodate more species and their respective gene and BAC maps, in addition to chromosome painting data. Chromhome application provides a single-page interface (SPI) with desktop style layout, delivering a better and richer user experience.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Marsupial chromosome DNA content and genome size assessed from flow karyotypes: invariable low autosomal GC content.

Extensive chromosome homologies revealed by cross-species chromosome painting between marsupials have suggested a high level of genome conservation during evolution. Surprisingly, it has been reported that marsupial genome sizes vary by more than 1.2 Gb between species. We have shown previously that individual chromosome sizes and GC content can be measured in flow karyotypes, and have applied this method to compare four marsupial species. Chromosome sizes and GC content were calculated for the grey short-tailed opossum (2n = 18), tammar wallaby (2n = 16), Tasmanian devil (2n = 14) and fat-tailed dunnart (2n = 14), resulting in genome sizes of 3.41, 3.31, 3.17 and 3.25 Gb, respectively. The findings under the same conditions allow a comparison between the four species, indicating that the genomes of these four species are 1-8% larger than human. We show that marsupial genomes are characterized by a low GC content invariable between autosomes and distinct from the higher GC content of the marsupial × chromosome

The evolution of imprinting: chromosomal mapping of orthologues of mammalian imprinted domains in monotreme and marsupial mammals.

BACKGROUND: The evolution of genomic imprinting, the parental-origin specific expression of genes, is the subject of much debate. There are several theories to account for how the mechanism evolved including the hypothesis that it was driven by the evolution of X-inactivation, or that it arose from an ancestrally imprinted chromosome. RESULTS: Here we demonstrate that mammalian orthologues of imprinted genes are dispersed amongst autosomes in both monotreme and marsupial karyotypes. CONCLUSION: These data, along with the similar distribution seen in birds, suggest that imprinted genes were not located on an ancestrally imprinted chromosome or associated with a sex chromosome. Our results suggest imprinting evolution was a stepwise, adaptive process, with each gene/cluster independently becoming imprinted as the need arose.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Construction of a highly enriched marsupial Y chromosome-specific BAC sub-library using isolated Y chromosomes

The Y chromosome is perhaps the most interesting element of the mammalian genome but comparative analysis of the Y chromosome has been impeded by the difficulty of assembling a shotgun sequence of the Y. B AC-based sequencing has been successful for the human and chimpanzee Y but is difficult to do efficiently for an atypical mammalian model species (Skaletsky et al. 2003, Kuroki et al. 2006). We show how Y-specific sub-libraries can be efficiently constructed using DNA amplified from microdissected or flow-sorted Y chromosomes. A Bacterial Artificial Chromosome (BAC) library was constructed from the model marsupial, the tammar wallaby (Macropus eugenii). We screened this library for Y chromosome-derived BAC clones using DNA from both a microdissected Y chromosome and a flow-sorted Y chromosome in order to create a Y chromosome-specific sub-library. We expected that the tammar wallaby Y chromosome should detect ∼100 clones from the 2.2 times redundant library. The microdissected Y DNA detected 85 clones, 82% of which mapped to the Y chromosome and the flow-sorted Y DNA detected 71 clones, 48% of which mapped to the Y chromosome. Overall, this represented a ∼330-fold enrichment for Y chromosome clones. This presents an ideal method for the creation of highly enriched chromosome-specific sub-libraries suitable for BAC-based sequencing of the Y chromosome of any mammalian species

Extensive Karyotype Reorganization in the Fish Gymnotus arapaima (Gymnotiformes, Gymnotidae) Highlighted by Zoo-FISH Analysis.

The genus Gymnotus (Gymnotiformes) contains over 40 species of freshwater electric fishes exhibiting a wide distribution throughout Central and South America, and being particularly prevalent in the Amazon basin. Cytogenetics has been an important tool in the cytotaxonomy and elucidation of evolutionary processes in this genus, including the unraveling the variety of diploid chromosome number (2n = from 34 to 54), the high karyotype diversity among species with a shared diploid number, different sex chromosome systems, and variation in the distribution of several Repetitive DNAs and colocation and association between those sequences. Recently whole chromosome painting (WCP) has been used for tracking the chromosomal evolution of the genus, showing highly reorganized karyotypes and the conserved synteny of the NOR bearing par within the clade G. carapo. In this study, painting probes derived from the chromosomes of G. carapo (GCA, 2n = 42, 30 m/sm + 12 st/a) were hybridized to the mitotic metaphases of G. arapaima (GAR, 2n = 44, 24 m/sm + 20 st/a). Our results uncovered chromosomal rearrangements and a high number of repetitive DNA regions. From the 12 chromosome pairs of G. carapo that can be individually differentiated (GCA1-3, 6, 7, 9, 14, 16, and 18-21), six pairs (GCA 1, 9, 14, 18, 20, 21) show conserved homology with GAR, five pairs (GCA 1, 9, 14, 20, 21) are also shared with cryptic species G. carapo 2n = 40 (34 m/sm + 6 st/a) and only the NOR bearing pair (GCA 20) is shared with G. capanema (GCP 2n = 34, 20 m/sm + 14 st/a). The remaining chromosomes are reorganized in the karyotype of GAR. Despite the close phylogenetic relationships of these species, our chromosome painting studies demonstrate an extensive reorganization of their karyotypes

Multiple rearrangements in cryptic species of electric knifefish, Gymnotus carapo (Gymnotidae, Gymnotiformes) revealed by chromosome painting.

BACKGROUND: Gymnotus (Gymnotidae, Gymnotiformes) is the Neotropical electric fish genus with the largest geographic distribution and the largest number of species, 33 of which have been validated. The diploid number varies from 2n = 39-40 to 2n = 54. Recently we studied the karyotype of morphologically indistinguishable samples from five populations of G. carapo sensu stricto from the Eastern Amazon of Brazil. We found two cytotypes, 2n = 42 (30 M/SM + 12 ST/A) and 2n = 40 (34 M/SM + 6 ST/A) and we concluded that the differences between the two cryptic species are due to pericentric inversions and one tandem fusion. RESULTS: In this study we use for the first time, whole chromosome probes prepared by FACS of the Gymnotus carapo sensu strictu species, cytotype with 2n = 42. Using two color hybridizations we were able to distinguish pairs 1, 2, 3, 7, 9, 14, 16, 18, 19, 20 and 21. It was not possible to separate by FACS and distinguish each of the following chromosome pairs even with dual color FISH: {4,8}; {10,11}; {5,6,17}; {12,13,15}. The FISH probes were then used in chromosome painting experiments on metaphases of the 2n = 40 cytotype. While some chromosomes show conserved synteny, others are rearranged in different chromosomes. Eight syntenic associations were found. CONCLUSIONS: These results show that the karyotype differences between these cryptic species are greater than assumed by classical cytogenetics. These data reinforce the previous supposition that these two cytotypes are different species, despite the absence of morphological differences. Additionally, the homology of repetitive DNA between the two provides evidence of recent speciation.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are