A Study on Variations of HDL Levels in Female vs. Male Mice The Battle of the Sexes: Presented by: Sean Roney Teresa Leslie Courtney Deshayes

QTL- Quantitative Trait Locus 2+ strains, phenotypic data vs. genotypic data Summarizes action, interaction, number, and precise location of regions Can compare with knockout and over expression What in the World is QTL-

HDL vs. LDL HDL- helps prevent cardiovascular disease Cardiovascular disease- hardening of the arteries The Basic Background-

Same environment, variation in plasma lipoprotein concentration – Genetic Background Nutrition, “safe” high-fat diet – Similar to humans Male vs. Female – Is sex a factor? – Compared two studies Experimental Factors-

Actual Experiment- Two Studies – 330 male R111x129 – 294 female B6x129 Length – 12 weeks (male) and 14 weeks (female) Plasma lipoprotein levels (HDL) in mice

Initial HDL Levels- Sex:nPlasma HDL mg/dl Female /- 1 Male /- 2 Males higher HDL levels, testosterone -- Difference of about 62 mg/dl Comparison- human females higher than males

Male QTLs ↑ Female QTLs ↓ QTL Analysis-

Table of Data- Sex:# Sig QTLs Hdlq5Hdlq14Hdlq15Hdlq16Hdlq17Hdlq18Hdlq19 Male3 XXX Female6 XXXXXX LOD scores range from Only HDL QTLs compared

Results- Male- Hdlq5 candidate gene APOA2 Female- Hdlq15 (interacts with Hdlq 14 and 19) APOA2 Information relatable to humans Confirmed with knockout and over expression methods

Other Findings- Female- – Hdlq18 is novel – Hdlq16 leads to gene involved with lipoprotein metabolism Both- – Hdlq17 APOA1/APOC3/APOA4 – Male outside the 95% CI

Conclusion- Males and females have some comparable data Females have several QTLs that males do not, investigate further Information is relatable to humans

References- Malcolm A. Lyons, Ron Korstanje, Renhua Li, Kenneth A. Walsh, Gary A. Churchill, Martin C. Carey, and Beverly Paigen. “Genetic contributors to lipoprotein cholesterol levels in an intercross of 129S1/SvImJ and RIIIS/J inbred mice.” Physiol Genomics 17: , First published Feb 10, Ishimori, Naoki, Renhua Li, Peter M. Kelmenson, Ron Korstanje, Kenneth A. Walsh, Gary A. Churchill, Kristina Forsman-Semb, and Beverly Paigen. "Quantitative Trait Loci Analysis for Plasma HDL-Cholesterol Concentrations and Atherosclerosis Susceptibility Between Inbred Mouse Strains C57BL/6J and 129S1/SvImJ." Arteriosclerosis, Thrombosis, and Vascular Biology 24 (2003): Miles, C. & Wayne, M. (2008) Quantitative trait locus (QTL) analysis. Nature Education 1(1) Some homology data for this paper were retrieved from the Mouse Genome Database (MGD), Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web (URL: (June 9, 2010)

A Monumental Thanks to- Randy Von Smith, PhD Tobias Beckwith Brook Milligan, PhD Jackson Laboratories NIH- RISE Program