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
Feb 24, 2016
A Study on Variations of HDL Levels in Female vs. Male Mice
The Battle of the Sexes:
Presented by:Sean Roney
Teresa LeslieCourtney 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: n Plasma HDL mg/dl
Female 294 81 +/- 1
Male 330 143 +/- 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
Hdlq5 Hdlq14 Hdlq15 Hdlq16 Hdlq17 Hdlq18 Hdlq19
Male 3 X X X
Female 6 X X X X X X
• 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.” 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