Genetic control of lipoprotein phenotypes in the laboratory opossum, Monodelphis domestica

Abstract

Introduction Monodelphis (Monodelphis domestica) shows 20-fold differences, that may be under genetic control, in individual responses to a high-fat challenge diet.

Materials and methods

Two partially inbred lines of animals were derived by selectively breeding among high responders and low responders and we analysed data from these pedigreed animals and their F₁ progeny. A blood sample was taken from each animal while consuming the basal diet (basal sample). Each animal was then fed a high-fat, high-cholesterol challenge diet for 8 weeks prior to collection of a second blood sample (challenge sample). Lipoprotein measurements included cholesterol concentrations of high-density lipoproteins (HDL-C) and low-density lipoproteins (non-HDL-C) and particle size phenotypes for both.

Results

Quantitative genetic analyses indicated strong heritabilities (range, 0.382–0.827) for each of the eight traits. We also tested for single genes with large effects on each trait (major genes). Segregation analyses provided evidence of major genes for three traits: basal non-HDL-C, challenge non-HDL-C, and challenge HDL-C; no major genes were detected for the lipoprotein size traits. Tests for pleiotropy, using bivariate one-locus segregation analyses, showed that the major locus for challenge HDL-C had no effect on the basal HDL-C and that the major locus for challenge non-HDL-C had no effect on basal non-HDL-C. However, the major gene for basal non-HDL-C did significantly influence challenge non-HDL-C.

Conclusion

We have found evidence for at least three genes influencing lipoprotein phenotypes under two dietary regimes. Identification of these genes may provide valuable insights into lipoprotein metabolism in other species, including man.