ABSTRACT
A first-generation radiation hybrid (RH) map of the equine (Equus caballus) genome was assembled using 92 horse x hamster hybrid cell lines and 730 equine markers. The map is the first comprehensive framework map of the horse that (1) incorporates type I as well as type II markers, (2) integrates synteny, cytogenetic, and meiotic maps into a consensus map, and (3) provides the most detailed genome-wide information to date on the organization and comparative status of the equine genome. The 730 loci (258 type I and 472 type II) included in the final map are clustered in 101 RH groups distributed over all equine autosomes and the X chromosome. The overall marker retention frequency in the panel is approximately 21%, and the possibility of adding any new marker to the map is approximately 90%. On average, the mapped markers are distributed every 19 cR (4 Mb) of the equine genome--a significant improvement in resolution over previous maps. With 69 new FISH assignments, a total of 253 cytogenetically mapped loci physically anchor the RH map to various chromosomal segments. Synteny assignments of 39 gene loci complemented the RH mapping of 27 genes. The results added 12 new loci to the horse gene map. Lastly, comparison of the assembly of 447 equine genes (256 linearly ordered RH-mapped and additional 191 FISH-mapped) with the location of draft sequences of their human and mouse orthologs provides the most extensive horse-human and horse-mouse comparative map to date. We expect that the foundation established through this map will significantly facilitate rapid targeted expansion of the horse gene map and consequently, mapping and positional cloning of genes governing traits significant to the equine industry.
Subject(s)
Conserved Sequence/genetics , Genome, Human , Genome , Horses/genetics , Radiation Hybrid Mapping/methods , Radiation Hybrid Mapping/veterinary , Animals , Cell Line , Cricetinae , Genetic Markers/genetics , Genetic Markers/radiation effects , Humans , Hybrid Cells , In Situ Hybridization, Fluorescence/methods , In Situ Hybridization, Fluorescence/statistics & numerical data , In Situ Hybridization, Fluorescence/veterinary , Mice , Microsatellite Repeats/genetics , Microsatellite Repeats/radiation effects , Molecular Sequence Data , Radiation Hybrid Mapping/statistics & numerical data , Sequence Alignment/methods , Sequence Alignment/statistics & numerical data , Sequence Alignment/veterinary , Statistical Distributions , Synteny/genetics , Synteny/radiation effectsABSTRACT
MOTIVATION: Radiation Hybrid Mapping (RHM) is a technique used to order a set of markers on a genome and estimating physical distances between them. RHM provides information on marker placement independent from other methods such as sequencing, and can therefore be used for example in genome sequencing to help ordering contigs. A radiation hybrid framework can be constructed by choosing a set of markers so that the chromosome coverage is good and so that the markers can be ordered with high confidence. Automatically constructing RHM frameworks is a computationally challenging problem. RESULTS: We have developed a new method for constructing radiation hybrid frameworks. Given a relatively large set of markers for a chromosome, the algorithm aims to select an ordered subset that makes up a framework, and that contains as many markers as possible. The algorithm has a time complexity that is better than any of the existing methods that we are aware of. Furthermore, we propose a method for comparing if two frameworks are consistent, giving a visual presentation as well as quantitative measures of how well the two frameworks agree. Applying our method on marker sets from 22 human chromosomes and comparing the resulting frameworks with previously published frameworks, we demonstrate that our automatic method efficiently constructs frameworks with good coverage of each chromosome and with high degree of agreement on the marker ordering.
Subject(s)
Radiation Hybrid Mapping/methods , Algorithms , Chromosomes, Human/genetics , Computational Biology , Databases, Genetic , Genetic Markers , Humans , Radiation Hybrid Mapping/statistics & numerical dataABSTRACT
This unit opens with a comparison of radiation hybrid and somatic cell hybrid analyses. Definitions, assumptions, and a mathematical model for radiation hybrid analysis are presented. In addition, parametric and nonparametric methods of data analysis are presented.
Subject(s)
Radiation Hybrid Mapping/statistics & numerical data , Animals , Data Interpretation, Statistical , Genetics, Medical , Humans , Hybrid Cells , Likelihood Functions , Models, Theoretical , Proportional Hazards Models , Software , Statistics, NonparametricABSTRACT
Several panels are available for puchase, and this unit provides update information on the use of the three commercially available panels and on the interpretation of mapping results using the Internet. Radiation hybrid panels continue to serve as integral biological reagents in physical mapping projects and positional cloning.
