The Battle of the Sexes:

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

What in the World is QTL-

• 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

The Basic Background-

HDL- helps prevent cardiovascular disease

HDL vs. LDL Cardiovascular disease-

hardening of the arteries

Experimental Factors-

• 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

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:

Female Male

n

294 330

Plasma HDL mg/dl

81 +/- 1 143 +/- 2 • Males higher HDL levels, testosterone - Difference of about 62 mg/dl • Comparison- human females higher than males

QTL Analysis-

Male QTLs ↑ Female QTLs ↓

Table of Data-

• LOD scores range from 2.6-9.8

• Only HDL QTLs compared

Sex:

Male Female

# Sig QTLs

3 6

Hdlq5

X

Hdlq14 Hdlq15 Hdlq16 Hdlq17 Hdlq18 Hdlq19

X X X X X X X X

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 17:114-121, 2004. First

published Feb 10, 2004.

• 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): 161-66.

• 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: http://www.informatics.jax.org). (June 9, 2010)

A Monumental Thanks to-

• Randy Von Smith, PhD • Tobias Beckwith • Brook Milligan, PhD • Jackson Laboratories • NIH- RISE Program