Poster 27
Presenter: Luanne Peters
Wednesday, 3:00 – 5:00pm

Identification of QTL for Hematological Traits in Diversity Outbred Mice

Luanne L. Peters, Daniel M. Gatti, Karen L. Svenson, and Gary A. Churchill
The Jackson Laboratory

Studies in multiple species reveal that a significant genetic component underlies baseline peripheral blood traits including hemoglobin (Hgb); hematocrit (Hct); red cell indices; total red cell, white cell, and platelet counts; and cell volumes. Baseline peripheral blood traits are independent risk factors for complex human diseases with considerable morbidity and mortality. Previously, we identified multiple QTL for these and other peripheral blood parameters using twelve traditional 2-progenitor crosses. However, with rare exception, confidence intervals were exceedingly large. Here, we used 647 Diversity Outbred mice (G4-G7) to map peripheral blood traits obtained using an Advia whole blood analyzer equipped with mouse-specific software. Data were analyzed using QTL/REL with modifications to accommodate the 8-founder origin of DO mice. Significance levels were determined by permutation. There was a high concordance of QTL identified in DO and F2 mice. For example, of 22 loci related to erythroid traits detected in DO mice, 16 were previously detected in F2 intercrosses, including the large effect Chr 7 cell hemoglobin concentration mean (CHCM, analogous the MCHC) QTL, Chcmq3. Confidence intervals, which on average were many cM in conventional crosses, were much smaller in the DO population. For example, the smallest interval for Chcmq3 obtained in conventional crosses was 11 Mb. In the DO population, it was 0.9 Mb. Notably, for both erythroid and white blood cell traits, highly correlated measures (e.g., Hgb, Hct) mapped to the same loci, which allows for combined analyses. Candidate genes for these loci are currently being assessed.