CXB Genotypes Database (July 2005)
Summary:
This CXB genotype data set still consists of 1384 SNP and microsatellite markers with unique strain distribution patterns. This file is used to map all CXB phenotype data sets including approximately 500 phenotypes in the CXB Phenotypes database and 45,000 Hippocampal mRNA expression phenotypes. The present genotype file supercedes an older microsatellite file (405 markers).
About the genotypes used in these studies:
WebQTL mapping algorithms rely on genotypes for the CXB strains that include both microsatellite markers (labeled Mit and Msw) and single nucleotide polymorphisms (labeled Gnf). The current set of markers (n = 1384) have been carefully error-checked. Closely linked genetic markers often have the same strain distribution pattern (SDP) across the CXB strains. For computational efficiency, we only use a single marker associated with each SDP. The CXB set is so small that markers on different chromosomes occasionally have almost precisely the same SDP. This produces high non-syntenic association and false linkage between variance in phenotypes and genotypes. Please examine the correlation coeffients of markers close to interest loci with ALL other markers to evaluate the risk of non-syntenic association.
We have genotyped all available CXB strains from The Jackson Laboratory. The entire CXB genotypes data may be downloaded.
Marker-strain pairs for which we were missing genotypes were often inferred from flanking markers. In marker sets lacking genotypes for a particular strain, a note is included to that effect in the marker set description below.
About the marker sets:
Mit
Mit markers, described by William Dietrich and colleagues (1992), are the most widely used of the three marker sets. These markers typically consist of regions of repeated dinucleotides (so-called CA repeat microsatellites) that vary in length among strains. The CA repeat polymorphisms are flanked by unique sequence that can be used to design polymerase chain reaction (PCR) primers that will selectively amplify the intervening variable region. While many of the Mit markers have been typed in the BXD strain set by a number of investigators, the genotypes used here are those reported in the consensus map created by Williams and colleagues (2001).
Mit marker names: D + (Chr of Marker) + Mit + (Order Found)
- D indicates that the marker is a DNA segment.
- Mit indicates that the marker was identified at the Massachusetts Institute of Technology.
- Order Found indicates the order in which the markers were identified.
Gnf
Gnf markers are single nucleotide polymorphisms (SNPs) identified between B6 and D2 by genomic sequence sampling. Polymorphisms were typed by Mathew Pletcher and Tim Wiltshire using the Sequenom MassEXTEND system (Wiltshire et al., 2003). Each of the genotyping reactions was set up in duplicate. Physical positions were determined for each marker and integrated with previous BXD RI mapping data based on a combination of physical and genetic positions. Unsupported double crossovers were verified by manual inspection to ensure accuracy of calls. A full list of SNPs identified in the sequence sampling can be found at http://www.gnf.org/SNP.
Gnf marker names: S + (Chr of Marker) + Gnf + (Mb position)
- S indicates the marker is a SNP
- Gnf indicates that the marker originated at the Genomics Institute of the Novartis Research Foundation.
- Mb position may include decimal values.
Notes on Nomenclature: The CXB set is the first and oldest group of RI strains of any species. The materal strain is BALB/cBy and the paternal strain is C57BL/6By. Eleven CXB strains were produced at the National Institutes of Health by Donald Bailey (By) starting in 1959, and eight are still extant. After moving to The Jackson Laboratory in 1967, an additional set of five strains were created with the help of Jo Hilgers (Hi). The strains are now labeled numerically. The following are the old strain symbols for CXB1 through CXB7:
- CXB1 = CXBD
- CXB2 = CXBE
- CXB3 = CXBG
- CXB4 = CXBH
- CXB5 = CXBI
- CXB6 = CXBJ
- CXB7 = CXBK (has a 3' UTR polymorphism in mu opioid receptor; PMID: 16708053)
Acknowledgments:
Genotypes for the Mit and Msw marker sets were determined by Jing Gu and
Lu Lu. 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.
This text file was originally written by Jeremy Peirce (August 21,
2003). Updated August 22, 2003 by RW/JP/LL. Updated July 31, 2005 by RW.
Reference:
Dietrich WF, Katz H, Lincoln SE (1992) A genetic map of the mouse suitable for typing in intraspecific crosses. Genetics 131:423-447.
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.
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