Automated Construction of High-Density Comparative Maps Between Rat, Human, and Mouse

Autor: Simon N. Twigger, Todd E. Scheetz, M. Bento Soares, Marcelo A. Nobrega, Masahide Shiozawa, Yongjian Samuel Cheng, Dan Chen, Peter J. Tonellato, Val C. Sheffield, Thomas L. Casavant, Monika Stoll, Anne E. Kwitek, Howard J. Jacob, Jo Gullings-Handley
Rok vydání: 2001
Předmět:
Zdroj: Genome Research. 11:1935-1943
ISSN: 1549-5469
1088-9051
Popis: Over the past 200 years, animal models have been selected and used primarily as surrogates for humans. The primary selection criteria for the animal models have been disease-based phenotypic characteristic(s) similar to those of humans. Indeed, many rat and mouse models share pathobiological characteristics similar to a human condition (Desnick et al. 1982). The idea that genomic organization also tends to be evolutionarily conserved between species was postulated in the early 1900s (Castle and Wachter 1924; Haldane 1927). Studies involving banding conservation and chromosome painting (ZOO-FISH) have since shown that large stretches of DNA are conserved in mammalian species as divergent as humans and fin whales (Nash and O'Brien 1982; Sawyer and Hozier 1986; Scherthan et al. 1994; Weinberg and Stanyon 1995). Although these studies showed genome conservation, they could not show the explicit conserved gene order at high resolution; such detail can only be accomplished at the genetic/physical mapping or sequence level. Several studies evaluating genome conservation at the genetic and physical mapping level have determined that gene order does tend to be conserved between mammals (Oakey et al. 1992; Sellar et al. 1994; Stubbs et al. 1994), opening up the prospect of constructing comparative maps between multiple species based on genetic sequence and map information (Nadeau 1989; Anderson et al. 1996; DeBry and Seldin 1996; Lyons 1997). As genetic and physical maps of human and model organisms developed with the advent of the Human Genome Project in the 1990s and as the number of identified genes increased, the number of possible integration points dramatically enhanced the potential quality and density of comparative maps (O'Brien et al. 1999). The increased number of mapped genes and expressed sequence tag (EST) sites has led to sequence comparisons to identify orthologous genes (homologous genes in different species evolving from the same common ancestral gene; Clark 1999; Fitch 2000). When mapped in both species, these orthologs serve as anchors that are useful in identifying conserved segments between species. However, until absolute phylogeny of the genes is truly known, the ortholog assignments between these species must be considered preliminary; thus, it is prudent to assign gene-based anchors using the more conservative homolog relationships. The Mouse Genome Informatics (MGI) group at The Jackson Laboratories (http://www.informatics.jax.org/; Blake et al. 2000) has curated and assigned 2105 rat-mouse (R-M), 1950 rat-human (R-H), and 5603 mouse-human (M-H) orthologs. However, fewer of these genes have been mapped across all three species, limiting the number of anchors for building comparative maps. Several lower-resolution comparative maps have been generated between rat, mouse, and human using fluorescence in situ hybridization (Levan et al. 1991; Scalzi and Hozier 1998; Grutzner et al. 1999) and combined genetic/radiation hybrid (RH) maps (Watanabe et al. 1999), the later identifying 522 anchor points between rat and human and/or mouse. The combined genetic/RH maps identified 41 conserved segments (identified by containing at least two homologous genes) between rat and mouse and 89 between rat and human (Watanabe et al. 1999). Using the analytical methodology developed by Nadeau and Taylor (1984), Watanabe et al. (1999) predicted the number of evolutionarily conserved segments between rat and human to be 152+21 and between rat and mouse to be 49+7. The emergence of the RH maps in human, rat, and mouse (Gyapay et al. 1996; Steen et al. 1999; VanEtten et al. 1999), coupled with the development of large numbers of UniGenes and ESTs for all three species, has revolutionized the way comparative maps can be built and maintained, before the complete genome sequencing of all three species. Indeed, the mapping approach described here can easily be extended to other mammals with significant EST libraries and RH maps and with entire genome sequences that will not likely be determined. There are many advantages of using the RH maps over curated or integrated genetic maps. First, RH mapping facilitates the integration of genetic markers, genes, and ESTs onto a single backbone map. Second, anchor (homology and map) assignments (based on sequence alignment, UniGene assemblies of ESTs, and map information) between species provide large numbers of hooks on and between the RH maps of rat, mouse, and human, which are useful for further sequence-based annotation of finished sequence from any source and, in particular, annotation of gene function based on results in animal models. Finally, the backbone of the maps has been developed and constructed using sequence-based comparison assignments coupled to a sophisticated scoring algorithm to choose the most likely homologies, thus providing an algorithm for de novo construction of comparative maps as the fundamental EST, gene assembly (UniGene or other), and RH map data sets mature. As the genomic sequence for human and mouse are in finishing and the sequencing of the rat is underway (Marshall 2000; Pennisi 2000a,b), such an RH-based scaffold becomes a powerful tool for early rat physical mapping, sequencing, and annotation of function. Comparative maps as described here provide a powerful platform for the integration of physiological and pharmacological information in the rat with genetic information in the mouse and clinical information in the human.
Databáze: OpenAIRE
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