A high resolution CEPH crossover mapping panel and integrated map of chromosome 11

Abstract

High resolution (0.1 cM) CEPH crossover mapping panels were constructed for chromosome 11. These panels will facilitate a transition from top-down physical and genetic mapping strategies to integrated breakpoint mapping strategies. Novel methods, which differ from other methods in overcoming the limitations of incomplete heterozygosity and variable marker density, were developed for creating the panels and integrated maps. This made it possible to identify and sublocalize the majority of crossovers in 61 families. The panels were used to map 139 microsatellite markers. A semi-integrated map and a fully-integrated map were constructed by combining these data with data from CEPH 7.1 and then integrating data from the radiation hybrid (RH) map. Genetic lengths estimated from the mapping panels were similar to the estimates obtained when all recombinant and non-recombinant offspring were included (189.4 cM in females and 126.1 cM in males), indicating that genetic distances are stable at this high marker density. The maps have a cM density of 0.62. The distance between ordered markers is 1.39-2.92 cM depending on the criterion for order and the extent of map integration. The 2D maps provide the resolution and flexibility needed to enhance current applications such as positional cloning and mapping complex disorders; while the mapping panels will greatly improve the resolution, reliability and efficiency of future genetic mapping.

Eighteen new polymorphic markers in the multiple endocrine neoplasia type 1 (MEN1) region

“…However, we place D11S449 nearly 600 kb distal to PYGM. With this exception, the map order by Fain et al (1996) is consistent with our map order. The availability of the clone contig has now allowed for the precise ordering of markers such as D11S1266 which were not resolved in the 2-D map due to either lack of recombinants or RRH breaks.…”

“…An integrated genetic/RRH map (2-D map) for chromosome 11 (Fain et al 1996) provisionally placed D11S449 proximal to PYGM. However, we place D11S449 nearly 600 kb distal to PYGM.…”

Comparison of human genetic and sequence-based physical maps

“…We identified 19 recombination deserts up to 5 Mb in length with sex-average recombination rates below 0.3 cM Mb −1 , and 12 recombination jungles up to 6 Mb in length with sex-average recombination rates greater than 3.0 cM Mb −1 (see Supplementary Information). Wide variation in recombination rates across chromosomes has been observed previously for humans [8][9][10][11] and for other eukaryotic species [12][13][14][15] , and is clearly the rule rather than the exception.…”

Molecular Pathogenesis of Rhabdomyosarcoma

“…In the first column, a low resolution banding pattern of chromosome 11 is shown, with addition of the five sub-regions in band 11p15. In the second column, the status of these loci in two informative ERMS samples is shown such that filled circles indicate allelic loss, open circles indicate maintenance of heterozygosity, and shaded circles indicate non-informative loci 78,79 The third column shows a map of the 11p15 region derived from linkage mapping 80 and physical mapping studies. 34,35,81,82 The fourth column presents the positions of translocation breakpoints in BWS patients.…”