For all of the reasons discussed above, phenotypes must be characterized across a larger number of inbred strains to facilitate genetic discovery. Our acetaminophen toxicity study [17], where the only resistant inbred strain was not in our genetic database, indicates that many 21st century biomedical problems may not be solved using the inbred strains that were commonly studied in the 20th century. Each inbred strain has unique genetic variants, and possibly phenotypic responses, which could enable genetic discovery. Our simulated datasets indicate that genetic loci with an effect size as low as 0.15 could be identified if 40 inbred strains were analyzed [8], which would certainly overcome prior criticism that computational genetic mapping cannot analyze genes of small effect size [28]. Given the multiple factors that contribute to an under-estimation of the genetic effect size (discussed above), it is likely that many different phenotypes can be analyzed by HBCGM when a larger number of strains are characterized. Since additional strains must be genetically analyzed, the new computational tool was used to examine the impact that incorporating allelic data from an
