Abstract
BackgroundA number of different quantitative trait loci (QTL) for various phenotypic traits, including milk production, functional, and conformation traits in dairy cattle as well as growth and body composition traits in meat cattle, have been mapped consistently in the middle region of bovine chromosome 6 (BTA6). Dense genetic and physical maps and, ultimately, a fully annotated genome sequence as well as their mutual connections are required to efficiently identify genes and gene variants responsible for genetic variation of phenotypic traits. A comprehensive high-resolution gene-rich map linking densely spaced bovine markers and genes to the annotated human genome sequence is required as a framework to facilitate this approach for the region on BTA6 carrying the QTL.ResultsTherefore, we constructed a high-resolution radiation hybrid (RH) map for the QTL containing chromosomal region of BTA6. This new RH map with a total of 234 loci including 115 genes and ESTs displays a substantial increase in loci density compared to existing physical BTA6 maps. Screening the available bovine genome sequence resources, a total of 73 loci could be assigned to sequence contigs, which were already identified as specific for BTA6. For 43 loci, corresponding sequence contigs, which were not yet placed on the bovine genome assembly, were identified. In addition, the improved potential of this high-resolution RH map for BTA6 with respect to comparative mapping was demonstrated. Mapping a large number of genes on BTA6 and cross-referencing them with map locations in corresponding syntenic multi-species chromosome segments (human, mouse, rat, dog, chicken) achieved a refined accurate alignment of conserved segments and evolutionary breakpoints across the species included.ConclusionThe gene-anchored high-resolution RH map (1 locus/300 kb) for the targeted region of BTA6 presented here will provide a valuable platform to guide high-quality assembling and annotation of the currently existing bovine genome sequence draft to establish the final architecture of BTA6. Hence, a sequence-based map will provide a key resource to facilitate prospective continued efforts for the selection and validation of relevant positional and functional candidates underlying QTL for milk production and growth-related traits mapped on BTA6 and on similar chromosomal regions from evolutionary closely related species like sheep and goat. Furthermore, the high-resolution sequence-referenced BTA6 map will enable precise identification of multi-species conserved chromosome segments and evolutionary breakpoints in mammalian phylogenetic studies.
Highlights
A number of different quantitative trait loci (QTL) for various phenotypic traits, including milk production, functional, and conformation traits in dairy cattle as well as growth and body composition traits in meat cattle, have been mapped consistently in the middle region of bovine chromosome 6 (BTA6)
We found 95 % of all sequences mapped on our Radiation hybrid (RH) map to be presented in the current 6× coverage draft of the bovine genome sequence exemplarily underlining its high potential as a framework sequence resource to represent the molecular architecture of the bovine chromosomes
The high-resolution RH map for the defined region of BTA6 presented here integrates anonymous markers, expressed sequence tags (ESTs), and genes from currently available bovine linkage and RH maps as well as a high number of comparative anchor loci derived from orthologous HSA4
Summary
A number of different quantitative trait loci (QTL) for various phenotypic traits, including milk production, functional, and conformation traits in dairy cattle as well as growth and body composition traits in meat cattle, have been mapped consistently in the middle region of bovine chromosome 6 (BTA6). A comprehensive high-resolution gene-rich map linking densely spaced bovine markers and genes to the annotated human genome sequence is required as a framework to facilitate this approach for the region on BTA6 carrying the QTL. A high-resolution physical map will provide a basic framework to assist the final high-quality sequence assembly and annotation process of the bovine genome for anchoring genes, anonymous loci, WGS, BES, and preliminary contigs along bovine chromosomes. The availability of the complete architecture of bovine chromosomes will facilitate positional cloning efforts focusing on targeted identification of the causative sequence variation underlying quantitative trait loci (QTL) [5]. In order to construct a high-resolution map for a specific chromosome or targeted chromosomal region, comparative mapping information from maps of the annotated human and mouse genomes can be utilized efficiently. Considering all RH panels available for the bovine genome, the 12,000 rad whole genome RH panel (12 k WG-RH, [7]) has been shown to have the high mapping power required to create accurate maps of a highly elevated resolution in defined small chromosomal regions [8,9,10,11]
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