Figure 1. Genetic Mapping and Identification of the Plt8 Mutation.

(A) 90 PLT8 F₂ mice were genotyped with polymorphic microsatellite markers spread throughout the genome. The frequency of C57BL/6 homozygosity is plotted along the length of Chromosome 10 (filled circles) and Chromosome 11 (open circles). No mice were homozygous C57BL/6 across an interval on Chromosome 11 (arrows). PLT8 F₂ mice that carried C57BL/6 DNA (‘+/–') at this position had a higher mean platelet count than wildtype mice (a control F₂ population, *p < 0.002) or littermates that were homozygous 129/Sv (‘+/+').

(B) A 1.39-Mb candidate interval was defined between D11CAR28 and D11CAR48 (boxed in red). Genotyping is shown for individual recombinants (top panel); C57BL/6 homozygosity is represented by open boxes, heterozygous markers are gray and 129/Sv homozygosity is shown in black. A haplotype map is shown (bottom panel) that defines the same interval using the lethality phenotype; the number of mice with each haplotype is shown at left.

(C) DNA was extracted from PLT8 mice with elevated platelet counts for sequence analysis. A single base pair deletion was identified in heterozygous mice (Suz12^Plt8/+) and in homozygous tissue obtained from embryos (Suz12^Plt8/Plt8) (red arrow). The deletion disrupts the splice acceptor site upstream of exon 16.