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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
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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
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- • Males higher HDL levels, testosterone • -- Difference of about 62 mg/dl • Comparison- human females higher than males
QTL Analysis- Female QTLs ↓ Male QTLs ↑
Table of Data- • LOD scores range from 2.6-9.8 • 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.” PhysiolGenomics 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