We have completed a second-generation linkage map that incorporates sequence-based positional information. This new map, the Rutgers Map v.2, includes 28,121 polymorphic markers with physical positions corroborated by recombination-based data. Sex-averaged and sex-specific linkage map distances, along with confidence intervals, have been estimated for all map intervals. In addition, a regression-based smoothed map is provided that facilitates interpolation of positions of unmapped markers on this map. With nearly twice as many markers as our first-generation map, the Rutgers Map continues to be a unique and comprehensive resource for obtaining genetic map information for large sets of polymorphic markers.Accurate and comprehensive linkage maps continue to be critical for linkage analyses (Daw et al. 2000;Barber et al. 2006;Fingerlin et al. 2006;Dietter et al. 2007), positional cloning projects, and even for some aspects of genome-wide association analyses (Maniatis et al. 2002;Tapper et al. 2005). Previously, we constructed the first-generation combined linkage-physical map (Rutgers Map v.1; Kong et al. 2004) containing 14,759 markers, genotyped in a mixture of CEPH (Center d'Etude du Polymorphisme Humain) (Dausset et al. 1990) and deCODE (Kong et al. 2002) families. Now, we have pooled this data set with 13,666 singlenucleotide polymorphisms (SNPs) genotyped in the CEPH reference pedigrees at the companies Applied Biosystems, Affymetrix, and Illumina. We used the pooled data to construct a secondgeneration combined linkage-physical map (Rutgers Map v.2), which has nearly twice the number of markers and increased marker density relative to the Rutgers Map v.1. The physical positions of 28,121 markers were corroborated by recombinationbased data, making the Rutgers Map v.2, to our knowledge, the most dense and accurate linkage map of the human genome.The Rutgers Map v.2 also provides three novel features that are not generally offered by other publicly available maps. First, we have estimated approximate 95% confidence intervals for the size of all 24,145 map intervals, both on the sex-averaged and sex-specific maps. This feature may be useful for assessing sensitivity of an analysis to map uncertainty and for combining the information in the Rutgers Map v.2 with map estimates derived from independent studies. In addition, we have applied local regression to create a smoothed version of the Rutgers Map that separates all markers by non-zero map distances. Overall, this alternative map should provide better estimates of map distance since nearly half of the map intervals in the Rutgers Map v.2, while physically distinct, show no evidence of recombination. Third, the smoothed map facilitates interpolation of map positions for markers that are not on our map. For example, a cMscale map position can be easily estimated for any of the millions of SNP markers that have not been genotyped in the CEPH reference pedigrees and hence are not present on any of the CEPHbased linkage maps.
Results
Markers and genotype dataThe ...
