A high density linkage map of the bovine genome

<p>Abstract</p> <p>Background</p> <p>Recent technological advances have made it possible to efficiently genotype large numbers of single nucleotide polymorphisms (SNPs) in livestock species, allowing the production of high-density linkage maps. Such maps can be used for quality control of other SNPs and for fine mapping of quantitative trait loci (QTL) via linkage disequilibrium (LD).</p> <p>Results</p> <p>A high-density bovine linkage map was constructed using three types of markers. The genotypic information was obtained from 294 microsatellites, three milk protein haplotypes and 6769 SNPs. The map was constructed by combining genetic (linkage) and physical information in an iterative mapping process. Markers were mapped to 3,155 unique positions; the 6,924 autosomal markers were mapped to 3,078 unique positions and the 123 non-pseudoautosomal and 19 pseudoautosomal sex chromosome markers were mapped to 62 and 15 unique positions, respectively. The linkage map had a total length of 3,249 cM. For the autosomes the average genetic distance between adjacent markers was 0.449 cM, the genetic distance between unique map positions was 1.01 cM and the average genetic distance (cM) per Mb was 1.25.</p> <p>Conclusion</p> <p>There is a high concordance between the order of the SNPs in our linkage map and their physical positions on the most recent bovine genome sequence assembly (Btau 4.0). The linkage maps provide support for fine mapping projects and LD studies in bovine populations. Additionally, the linkage map may help to resolve positions of unassigned portions of the bovine genome.</p

Assignment of chromosomal locations for unassigned SNPs/scaffolds based on pair-wise linkage disequilibrium estimates

<p>Abstract</p> <p>Background</p> <p>Recent developments of high-density SNP chips across a number of species require accurate genetic maps. Despite rapid advances in genome sequence assembly and availability of a number of tools for creating genetic maps, the exact genome location for a number of SNPs from these SNP chips still remains unknown. We have developed a locus ordering procedure based on linkage disequilibrium (LODE) which provides estimation of the chromosomal positions of unaligned SNPs and scaffolds. It also provides an alternative means for verification of genetic maps. We exemplified LODE in cattle.</p> <p>Results</p> <p>The utility of the LODE procedure was demonstrated using data from 1,943 bulls genotyped for 73,569 SNPs across three different SNP chips. First, the utility of the procedure was tested by analysing the masked positions of 1,500 randomly-chosen SNPs with known locations (50 from each chromosome), representing three classes of minor allele frequencies (MAF), namely >0.05, 0.01<MAF ≤ 0.05 and 0.001<MAF ≤ 0.01. The efficiency (percentage of masked SNPs that could be assigned a location) was 96.7%, 30.6% and 2.0%; with an accuracy (the percentage of SNPs assigned correctly) of 99.9%, 98.9% and 33.3% in the three classes of MAF, respectively. The average precision for placement of the SNPs was 914, 3,137 and 6,853 kb, respectively. Secondly, 4,688 of 5,314 SNPs unpositioned in the Btau4.0 assembly were positioned using the LODE procedure. Based on these results, the positions of 485 unordered scaffolds were determined. The procedure was also used to validate the genome positions of 53,068 SNPs placed on Btau4.0 bovine assembly, resulting in identification of problem areas in the assembly. Finally, the accuracy of the LODE procedure was independently validated by comparative mapping on the hg18 human assembly.</p> <p>Conclusion</p> <p>The LODE procedure described in this study is an efficient and accurate method for positioning SNPs (MAF>0.05), for validating and checking the quality of a genome assembly, and offers a means for positioning of unordered scaffolds containing SNPs. The LODE procedure will be helpful in refining genome sequence assemblies, especially those being created from next-generation sequencing where high-throughput SNP discovery and genotyping platforms are integrated components of genome analysis.</p

Linkage mapping bovine EST-based SNP

BACKGROUND: Existing linkage maps of the bovine genome primarily contain anonymous microsatellite markers. These maps have proved valuable for mapping quantitative trait loci (QTL) to broad regions of the genome, but more closely spaced markers are needed to fine-map QTL, and markers associated with genes and annotated sequence are needed to identify genes and sequence variation that may explain QTL. RESULTS: Bovine expressed sequence tag (EST) and bacterial artificial chromosome (BAC)sequence data were used to develop 918 single nucleotide polymorphism (SNP) markers to map genes on the bovine linkage map. DNA of sires from the MARC reference population was used to detect SNPs, and progeny and mates of heterozygous sires were genotyped. Chromosome assignments for 861 SNPs were determined by twopoint analysis, and positions for 735 SNPs were established by multipoint analyses. Linkage maps of bovine autosomes with these SNPs represent 4585 markers in 2475 positions spanning 3058 cM . Markers include 3612 microsatellites, 913 SNPs and 60 other markers. Mean separation between marker positions is 1.2 cM. New SNP markers appear in 511 positions, with mean separation of 4.7 cM. Multi-allelic markers, mostly microsatellites, had a mean (maximum) of 216 (366) informative meioses, and a mean 3-lod confidence interval of 3.6 cM Bi-allelic markers, including SNP and other marker types, had a mean (maximum) of 55 (191) informative meioses, and were placed within a mean 8.5 cM 3-lod confidence interval. Homologous human sequences were identified for 1159 markers, including 582 newly developed and mapped SNP. CONCLUSION: Addition of these EST- and BAC-based SNPs to the bovine linkage map not only increases marker density, but provides connections to gene-rich physical maps, including annotated human sequence. The map provides a resource for fine-mapping quantitative trait loci and identification of positional candidate genes, and can be integrated with other data to guide and refine assembly of bovine genome sequence. Even after the bovine genome is completely sequenced, the map will continue to be a useful tool to link observable phenotypes and animal genotypes to underlying genes and molecular mechanisms influencing economically important beef and dairy traits

A second generation genetic map for rainbow trout (Oncorhynchus mykiss)

<p>Abstract</p> <p>Background</p> <p>Genetic maps characterizing the inheritance patterns of traits and markers have been developed for a wide range of species and used to study questions in biomedicine, agriculture, ecology and evolutionary biology. The status of rainbow trout genetic maps has progressed significantly over the last decade due to interest in this species in aquaculture and sport fisheries, and as a model research organism for studies related to carcinogenesis, toxicology, comparative immunology, disease ecology, physiology and nutrition. We constructed a second generation genetic map for rainbow trout using microsatellite markers to facilitate the identification of quantitative trait loci for traits affecting aquaculture production efficiency and the extraction of comparative information from the genome sequences of model fish species.</p> <p>Results</p> <p>A genetic map ordering 1124 microsatellite loci spanning a sex-averaged distance of 2927.10 cM (Kosambi) and having 2.6 cM resolution was constructed by genotyping 10 parents and 150 offspring from the National Center for Cool and Cold Water Aquaculture (NCCCWA) reference family mapping panel. Microsatellite markers, representing pairs of loci resulting from an evolutionarily recent whole genome duplication event, identified 180 duplicated regions within the rainbow trout genome. Microsatellites associated with genes through expressed sequence tags or bacterial artificial chromosomes produced comparative assignments with tetraodon, zebrafish, fugu, and medaka resulting in assignments of homology for 199 loci.</p> <p>Conclusion</p> <p>The second generation NCCCWA genetic map provides an increased microsatellite marker density and quantifies differences in recombination rate between the sexes in outbred populations. It has the potential to integrate with cytogenetic and other physical maps, identifying paralogous regions of the rainbow trout genome arising from the evolutionarily recent genome duplication event, and anchoring a comparative map with the zebrafish, medaka, tetraodon, and fugu genomes. This resource will facilitate the identification of genes affecting traits of interest through fine mapping and positional cloning of candidate genes.</p