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
diseasehardening 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 LevelsSex:
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
QTL Analysis-
Female QTLs ↓
Male QTLs ↑
Table of Data• LOD scores range from 2.6-9.8
• Only HDL QTLs compared
Sex:
# Sig
QTLs
Male
3
Female
6
Hdlq5
Hdlq14
Hdlq15
Hdlq16
X
X
X
X
Hdlq17
Hdlq18
X
X
X
X
Hdlq19
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