BXD Genotypes Database
The BXD genotype file will be upgraded in mid 2009 using the new high density Affymetrix array developed in the laboratories of Drs. Fernando Pardo-Manuel de Villena (University of North Carolina) and Gary Churchill (The Jackson Laboratory). This cutting-edge research tool, produced and sold by Affymetrix, provides more than 100 times the SNP coverage than any other available mouse array, permitting high resolution mapping and genomic analysis.
JAX® Mouse Diversity Genotyping Array
New genotype array key features. This genotyping array can simultaneously assay over 620,000 phylogenetically informative SNPs. SNPs are spaced approximately one every 4.3kb across the genome and were selected to be highly polymorphic among characterized mouse strains. Genotypes called from analysis of the array data are highly reliable. From an internal study of two strains, genotypes from 99.7% of the polymorphic SNPs that had genotypes in the NCBI dbSNP database had matching genotypes from the Diversity Array.
The BXD genotype file used from June 2005 onward exploits a set of 3795 markers typed across 88 extant and extinct BXD strains (BXD1 through BXD100). This genotype file includes all markers, both SNPs and microsatellites, with unique strain distribution patterns (SDPs), as well as pairs of markers for those SDPs represented by two or more markers. In those situations where three or more markers had the same SDP, we retained only the most proximal and distal marker in the genotype file. This particular file has also been smoothed to eliminate genotypes that are likely to be erroneous. We have also conservatively imputed a small number of missing genotypes (usually over very short intervals). Smoothing genotypes is this way reduces the total number of SDPs and also lowers the rate of false discovery. However, this procedure also may eliminate some genuine SDPs.
The smoothed BXD genotype data file can be downloaded by ftp from
GeneNetwork at the URL http://www.genenetwork.org/genotypes/BXD.geno.
Source of Genotypes:
In collaboration with members of the CTC (Richard Mott, Jonathan Flint, and colleagues), we have helped genotype a total of 480 strains using a panel of 13,377 SNPs. These SNPs have been combined with our previious microsatellite genotypes to produce new consensus maps for the new expanded set of BXD using the latest mouse genome assembly as a reference frame for marker order (Mouse Build 36 - UCSC mm8). The order of markers given in the BXD genotype file is essentially the same as that given in Build 36. (Files were updated from mm6 to mm8 in January 2007.).
A total of 88 strains were genotyped using the full set of SNPs, and 7482 of these were informative. Informative in this sense simply means that the C57BL/6J and DBA/2J parental strains have different alleles. To reduce false positive errors when mapping using this ultra dense map, we have eliminated most single genotypes that generate double-recombinant haplotypes that are most commonly produced by typing errors ("smoothed" genotypes). For this reason, the genotypes used in the GeneNetwork differ from those downloaded directly from Richard Mott's web site at the Wellcome Trust, Oxford.
We have genotyped all available BXD strains from The Jackson Laboratory. BXD1 through BXD32 were produced by Benjamin Taylor starting in the late 1970s. BXD33 through BXD42 were produced by Taylor in the 1990s (Taylor et al., 1999). All BXD strains with numbers higher than BXD42 (BXD43 through BXD100) were generated by Lu Lu and Robert Williams at UTHSC, and by Jeremy Peirce and Lee Silver at Princeton University. We thank Guomin Zhou for generating the advanced intercross stock used to produce most of these advanced RI strains both at UTHSC and Princeton.
There are approximately 48 of these advanced BXD strains, each of which archives approximately twice the recombinations present in a typical F2-derived recombinant inbred strain (Peirce et al. 2003).
Due to the very high density of markers, the mapping algorithm used to map BXD data sets has been modified and is a mixture of simple marker regression, linear interpolation, and standard Haley-Knott interval mapping. When two adjacent markers have identical SDPs, they will have identical linkage statistics, as will the entire interval between these two markers (assuming complete and error-free haplotype data for all strains). On a physical map the LRS and the additive effect values will therefore be constant over this physical interval. Between neighboring markers that have different SDPs and that are separated by 1 cM or more, we use a conventional interval mapping method (Haley-Knott) combined with a Haldane estimate of genetic distance. When the interval is less than 1 cM, we simply interpolate linearly between markers based on a physical scale between those markers. The result of this mixture mapping algorithm is a linkage map of a trait that has an unusal profile that is particular striking on a physical (Mb) scale, with many plateaus, abrupt linear transitions between plateaus, and a few regions with the standard graceful curves typical of interval maps.
Archival BXD Genotype file: Prior to July 2005, the marker genotypes used to map all BXD data sets consisted of a set of 779 markers described by Williams and colleagues (2001) that also included a small number of additional SNPs from Tim Wiltshire and Mathew Pletcher (GNF, La Jolla), new microsatellite markers generated by Grant Morahan and Jing Gu (Msw type markers), and a few CTC markers by Jing Gu. This old marker data set was made obsolete by the ultra high density Illumina SNP genotype data generated Spring, 2005. The old genotype file is still available for use on the Archive site.
The entire BXD genotype data set used for mapping traits can be downloaded at www.genenetwork.org/genotypes/BXD.geno.
The great majority of SNP genotypes were generated at Illumina with support from the Wellcome Trust to JF and RM, a Human Brain Project grant to RWW (P20-MH 62009 and IBN-0003982), and by the NIAAA INIA Genotyping Core (U24AA13513). Genotypes for Mit and Msw markers were generated by Jing Gu and Lu Lu with support from NIH (P20-MH 62009). Markers for the Msw set were designed by Grant Morahan, Keith Satterley. Gnf SNP genotypes were generated by Tim Wiltshire and Mathew Pletcher. The selection of markers to included in the final file was carried out by Jing Gu and Robert W. Williams.
Dietrich WF, Katz H, Lincoln SE (1992) A genetic map of the mouse suitable for typing in intraspecific crosses. Genetics 131:423-447.
Taylor BA, Wnek C, Kotlus BS, Roemer N, MacTaggart T, Phillips SJ (1999) Genotyping new BXD recombinant inbred mouse strains and comparison of BXD and consensus maps.
Mamm Genome 10:335-348.
Williams RW, Gu J, Qi S, Lu L (2001) The genetic structure of recombinant inbred mice: High-resolution consensus maps for complex trait analysis. Genome Biology 2:RESEARCH0046
Wiltshire T, Pletcher MT, Batalov S, Barnes SW, Tarantino LM, Cooke MP, Wu H, Smylie K, Santrosyan A, Copeland NG, Jenkins NA, Kalush F, Mural RJ, Glynne RJ, Kay SA, Adams MD, Fletcher CF (2003) Genome-wide single-nucleotide polymorphism analysis defines haplotype patterns in mouse. Proc Natl Acad Sci USA 100:3380-3385.
This text file was originally written by Jeremy Peirce (August 21, 2003). Updated August 22, 2003 by RW/JP/LL. Updated October 19, 2004 by RW. Updated extensively July 26, 2005 by RW.