23 Results
for author "Eric E. Schadt"
- Table 1Examples of genotypic frequencies resulting from different combinations of values for additive (a), dominance (d), and overdominance (h) parameters of the transmission ratio distortion model
Figure 1Performance of the Bayes factor (BF) for testing additive and dominance transmission ratio distortions (TRD) under null TRD departures. Stochastic simulation processes were used to generate 1000 populations with variable size ranging between 100 and 500 individuals. Genetic data were restricted to a single biallelic marker (alleles A1 and A2)with genotypic frequencies of 0.25 (A1A1), 0.5 (A1A2), and 0.25 (A2A2). For each population, genetic data were analyzed under the BF approach developed above and by launching a unique Monte Carlo Markov chain of 100,000 elements; the first 10,000 iterations were discarded as burn-in. Moreover, TRD was also tested by applying a standard χ2-test with 2 d.f. Pairwise relationships are plotted, involving four parameters from the Bayesian analysis, i.e., BFs for additive (elements A, C, and E) and dominance (elements B, C, and F) TRD and posterior means of the additive (elements D and E) and dominance (elements D and F) effects, as well as the P-value (elements A and B) derived from the frequentist χ2-test.
Figure 2Performance of the Bayes factor (BF) for testing additive and dominance transmission ratio distortions (TRD) under additive TRD departures. Stochastic simulation processes were used to generate 1000 populations with 250 individuals each. Genetic data restricted to a single biallelic marker (alleles A1 and A2) and genotypic frequencies were generated under an additive TRD effect ranging from 0 to 0.5. For each population, genetic data were analyzed under the BF approach and by launching a unique Monte Carlo Markov chain of 100,000 elements; the first 10,000 iterations were discarded as burn-in. Moreover, TRD was also tested by applying a standard χ2-test with 2 d.f. Pairwise relationships are plotted, involving four parameters from the Bayesian analysis, i.e., BFs for additive (elements A, C, and F) and dominance (elements B and C) TRD and posterior means of the additive (elements D–F) and dominance (element D) effects, the P-value (elements A and B) derived from the frequentist χ2-test, and the simulated (i.e., real) additive TRD effect (element E).
Figure 3Diagrams of transmission ratio distortion quantitative trait loci in C57BL/6J × CAST/EiJ (cross 1) (A) and C57BL/6Jhg/hg × CAST/EiJ (cross 2) (B) F2 crosses with 296 and 536 mice, respectively. (Top) Observed genotypic frequencies for C57BL/6J (or C57BL/6Jhg/hg) homozygous (solid line), heterozygous (line with dark shading), and CAST/EiJ homozygous (line with light shading) populations. (Middle) P-value from a SNP-by-SNP χ2-test with 2 d.f., evaluating the departure from the expected 0.25:0.5:0.25 genotypic frequencies in an F2 population (the horizontal dotted line shows the significance threshold after a Bonferroni correction with α = 0.05). (Bottom) Plot of the posterior odds (PO) for dominance transmission ratio distortion (i.e., parameter d). Note that the remaining TRD parameters did not provide >1 PO at any marker location in these mouse crosses.
Figure 4Diagrams of transmission ratio distortion quantitative trait loci in C57BL/6J × C3H/HeJ (cross 3) (A) and B6.apoE−/− × C3H.apoE−/− (cross 4) (B) F2 crosses with 209 and 322 mice, respectively. (Top) Observed genotypic frequencies for C3H/HeJ (or C3H.apoE−/−) homozygous (solid line), heterozygous (line with dark shading), and C57BL/6J (or B6.apoE−/−) homozygous (line with light shading) populations. (Middle) P-value from a SNP-by-SNP χ2-test with 2 d.f., evaluating the departure from the expected 0.25:0.5:0.25 genotypic frequencies in an F2 population (the horizontal dotted line shows the significance threshold after a Bonferroni correction with α = 0.05). (Bottom) Plot of the posterior odds (PO) for dominance transmission ratio distortion (i.e., parameter d). Note that the remaining TRD parameters did not provide >1 PO at any marker location in these mouse crosses.
Figure 5Diagrams of transmission ratio distortion quantitative trait loci in two C57BL/6ob/ob × BTBRob/ob F2 crosses with 477 (cross 5) (A) and 541 mice (cross 6) (B), respectively. (Top) Observed genotypic frequencies for BTBRob/ob homozygous (solid line), heterozygous (line with dark shading), and C57BL/6ob/ob homozygous (line with light shading) populations. (Middle) P-value from a SNP-by-SNP χ2-test with 2 d.f., evaluating the departure from the expected 0.25:0.5:0.25 genotypic frequencies in an F2 population (the horizontal dotted line shows the significance threshold after a Bonferroni correction with α = 0.05). (Bottom) Plots of the posterior odds (PO) for the dominance (A) and additive (B) transmission ratio distortion (i.e., parameters d and a, respectively). Note that the remaining models did not provide >1 PO at any marker location in these mouse crosses.- Table 2Summary of significant transmission ratio distortion (TRD) QTL in F2 mouse crosses
Figure 1.—Adjusted BIC difference for QTL Archive studies. Positive (negative) absolute differences equal to or exceeding 10 units are highlighted in blue (red); absolute differences smaller than 10 units are highlighted in green.