JAX Liver 6C Affy M430 2.0 (Jul11) MDP

JAX Liver 6C Affy M430 2.0 (Jul11) MDP

Accession number: GN359

Summary:

High-fat diets are associated with increased obesity and metabolic disease in mice and humans. Here we used analysis of variance (ANOVA) to scrutinize a microarray data set consisting of 10 inbred strains of mice from both sexes fed atherogenic high-fat and control chow diets. An overall F-test was applied to the 40 unique groups of strain-diet-sex to identify 15,288 genes with altered transcription. Bootstrapping k-means clustering separated these changes into four strain-dependent expression patterns, including two sex-related profiles and two diet-related profiles. Sex-induced effects correspond to secretion (males) or fat and energy metabolism (females), whereas diet-induced changes relate to neurological processes (chow) or immune response (high-fat). The full set of pairwise contrasts for differences between strains within sex (90 different statistical tests) uncovered 32,379 total changes. These differences were unevenly distributed across strains and between sexes, indicating that strain-specific responses to high-fat diet differ between sexes. Correlations between expression levels and 8 obesity-related traits identified 5,274 associations between transcript abundance and measured phenotypic endpoints. From this number, 2,678 genes are positively correlated with total cholesterol levels and associate with immune-related categories while 2,596 genes are negatively correlated with cholesterol and connect to cholesterol synthesis. Keywords: gene expression analysis, strain comparision, effect of dietary fat, sex-specific effects.

Overall Design:

One group of mice was fed an atherogenic high-fat (30% fat) diet containing cholic acid to increase fat uptake and another was fed a low-fat (6% fat) regular chow diet. Males and females from both diets were studied for mouse strains 129S1/SvImJ, A/J, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, I/LnJ, MRL/MpJ-Tnfrsf6lpr/J, NZB/BINJ, PERA/Ei, and SM/J. All strains were sacrificed between 11- and 13 weeks of age except for CAST and PERA, which were harvested after 50 weeks of age. CAST and PERA were subsequently removed from our analysis based on discrepant harvest age, but can be found in our database (see below). Three replicate animals were used for each combination of diet, strain, and sex, resulting in a total of 120 mice surveyed for gene expression.

Index	Sample ID	Strain ID	HF=high-fat (30% fat) 6C=low-fat (6% fat)	Replicate Animal
1	GSM264767	129S1/SvImJ	6C	Rep1
2	GSM264768	129S1/SvImJ	6C	Rep2
3	GSM264769	129S1/SvImJ	6C	Rep3
4	GSM264770	129S1/SvImJ	HF	Rep1
5	GSM264771	129S1/SvImJ	HF	Rep2
6	GSM264772	129S1/SvImJ	HF	Rep3
7	GSM264773	129S1/SvImJ	6C	Rep1
8	GSM264774	129S1/SvImJ	6C	Rep2
9	GSM264775	129S1/SvImJ	6C	Rep3
10	GSM264776	129S1/SvImJ	HF	Rep1
11	GSM264777	129S1/SvImJ	HF	Rep2
12	GSM264778	129S1/SvImJ	HF	Rep3
13	GSM264779	A/J	6C	Rep1
14	GSM264780	A/J	6C	Rep2
15	GSM264781	A/J	6C	Rep3
16	GSM264782	A/J	HF	Rep1
17	GSM264783	A/J	HF	Rep2
18	GSM264784	A/J	HF	Rep3
19	GSM264785	A/J	6C	Rep1
20	GSM264786	A/J	6C	Rep2
21	GSM264787	A/J	6C	Rep3
22	GSM264788	A/J	HF	Rep1
23	GSM264789	A/J	HF	Rep2
24	GSM264790	A/J	HF	Rep3
25	GSM264791	C57BL/6J	6C	Rep1
26	GSM264792	C57BL/6J	6C	Rep2
27	GSM264793	C57BL/6J	6C	Rep3
28	GSM264794	C57BL/6J	HF	Rep1
29	GSM264795	C57BL/6J	HF	Rep2
30	GSM264796	C57BL/6J	HF	Rep3
31	GSM264797	C57BL/6J	6C	Rep1
32	GSM264798	C57BL/6J	6C	Rep2
33	GSM264799	C57BL/6J	6C	Rep3
34	GSM264800	C57BL/6J	HF	Rep1
35	GSM264801	C57BL/6J	HF	Rep2
36	GSM264802	C57BL/6J	HF	Rep3
37	GSM264803	BALB/cJ	6C	Rep1
38	GSM264804	BALB/cJ	6C	Rep2
39	GSM264805	BALB/cJ	6C	Rep3
40	GSM264806	BALB/cJ	HF	Rep1
41	GSM264807	BALB/cJ	HF	Rep2
42	GSM264808	BALB/cJ	HF	Rep3
43	GSM264809	BALB/cJ	6C	Rep1
44	GSM264810	BALB/cJ	6C	Rep2
45	GSM264811	BALB/cJ	6C	Rep3
46	GSM264813	BALB/cJ	HF	Rep1
47	GSM264814	BALB/cJ	HF	Rep2
48	GSM264815	BALB/cJ	HF	Rep3
49	GSM264845	C3H/HeJ	6C	Rep1
50	GSM264846	C3H/HeJ	6C	Rep2
51	GSM264847	C3H/HeJ	6C	Rep3
52	GSM264848	C3H/HeJ	HF	Rep1
53	GSM264849	C3H/HeJ	HF	Rep2
54	GSM264850	C3H/HeJ	HF	Rep3
55	GSM264852	C3H/HeJ	6C	Rep1
56	GSM264853	C3H/HeJ	6C	Rep2
57	GSM264855	C3H/HeJ	6C	Rep3
58	GSM264856	C3H/HeJ	HF	Rep1
59	GSM264857	C3H/HeJ	HF	Rep2
60	GSM264858	C3H/HeJ	HF	Rep3
61	GSM264859	CAST/EiJ	6C	Rep1
62	GSM264861	CAST/EiJ	6C	Rep2
63	GSM264862	CAST/EiJ	6C	Rep3
64	GSM264863	CAST/EiJ	HF	Rep1
65	GSM264864	CAST/EiJ	HF	Rep2
66	GSM264865	CAST/EiJ	HF	Rep3
67	GSM264866	CAST/EiJ	6C	Rep1
68	GSM264867	CAST/EiJ	6C	Rep2
69	GSM264868	CAST/EiJ	6C	Rep3
70	GSM264869	CAST/EiJ	HF	Rep1
71	GSM264870	CAST/EiJ	HF	Rep2
72	GSM264871	CAST/EiJ	HF	Rep3
73	GSM264872	DBA/2J	6C	Rep1
74	GSM264873	DBA/2J	6C	Rep2
75	GSM264874	DBA/2J	6C	Rep3
76	GSM264875	DBA/2J	HF	Rep1
77	GSM264876	DBA/2J	HF	Rep2
78	GSM264877	DBA/2J	HF	Rep3
79	GSM264890	DBA/2J	6C	Rep1
80	GSM264891	DBA/2J	6C	Rep2
81	GSM264892	DBA/2J	6C	Rep3
82	GSM264893	DBA/2J	HF	Rep1
83	GSM264894	DBA/2J	HF	Rep2
84	GSM264895	DBA/2J	HF	Rep3
85	GSM264896	I/LnJ	6C	Rep1
86	GSM264897	I/LnJ	6C	Rep2
87	GSM264898	I/LnJ	6C	Rep3
88	GSM264899	I/LnJ	HF	Rep1
89	GSM264900	I/LnJ	HF	Rep2
90	GSM264901	I/LnJ	HF	Rep3
91	GSM264902	I/LnJ	6C	Rep1
92	GSM264903	I/LnJ	6C	Rep2
93	GSM264904	I/LnJ	6C	Rep3
94	GSM264905	I/LnJ	HF	Rep1
95	GSM264906	I/LnJ	HF	Rep2
96	GSM264907	I/LnJ	HF	Rep3
97	GSM264908	MRL/MpJ-Fas/J	6C	Rep1
98	GSM264909	MRL/MpJ-Fas/J	6C	Rep2
99	GSM264910	MRL/MpJ-Fas/J	6C	Rep3
100	GSM264912	MRL/MpJ-Fas/J	HF	Rep1
101	GSM264913	MRL/MpJ-Fas/J	HF	Rep2
102	GSM264914	MRL/MpJ-Fas/J	HF	Rep3
103	GSM264915	MRL/MpJ-Fas/J	6C	Rep1
104	GSM264916	MRL/MpJ-Fas/J	6C	Rep2
105	GSM264917	MRL/MpJ-Fas/J	6C	Rep3
106	GSM264918	MRL/MpJ-Fas/J	HF	Rep1
107	GSM264920	MRL/MpJ-Fas/J	HF	Rep2
108	GSM264921	MRL/MpJ-Fas/J	HF	Rep3
109	GSM264922	NZB/BlNJ	6C	Rep1
110	GSM264924	NZB/BlNJ	6C	Rep2
111	GSM264925	NZB/BlNJ	6C	Rep3
112	GSM264926	NZB/BlNJ	HF	Rep1
113	GSM264928	NZB/BlNJ	HF	Rep2
114	GSM264929	NZB/BlNJ	HF	Rep3
115	GSM264930	NZB/BlNJ	6C	Rep1
116	GSM264931	NZB/BlNJ	6C	Rep2
117	GSM264932	NZB/BlNJ	6C	Rep3
118	GSM264933	NZB/BlNJ	HF	Rep1
119	GSM264935	NZB/BlNJ	HF	Rep2
120	GSM264936	NZB/BlNJ	HF	Rep3
121	GSM265061	PERA/EiJ	6C	Rep1
122	GSM265062	PERA/EiJ	6C	Rep2
123	GSM265063	PERA/EiJ	6C	Rep3
124	GSM265064	PERA/EiJ	HF	Rep1
125	GSM265065	PERA/EiJ	HF	Rep2
126	GSM265066	PERA/EiJ	HF	Rep3
127	GSM265067	PERA/EiJ	6C	Rep1
128	GSM265068	PERA/EiJ	6C	Rep2
129	GSM265069	PERA/EiJ	6C	Rep3
130	GSM265070	PERA/EiJ	HF	Rep1
131	GSM265071	PERA/EiJ	HF	Rep2
132	GSM265072	PERA/EiJ	HF	Rep3
133	GSM265074	SM/J	6C	Rep1
134	GSM265075	SM/J	6C	Rep2
135	GSM265105	SM/J	6C	Rep3
136	GSM265217	SM/J	HF	Rep1
137	GSM265248	SM/J	HF	Rep2
138	GSM265275	SM/J	HF	Rep3
139	GSM265324	SM/J	6C	Rep1
140	GSM265331	SM/J	6C	Rep2
141	GSM265357	SM/J	6C	Rep3
142	GSM265358	SM/J	HF	Rep1
143	GSM265359	SM/J	HF	Rep2
144	GSM265360	SM/J	HF	Rep3

Citations:

Burgess-Herbert SL, Cox A, Tsaih SW, Paigen B. Practical applications of the bioinformatics toolbox for narrowing quantitative trait loci. Genetics 2008 Dec;180(4):2227-35. PMID: 18845850 Shockley KR, Witmer D, Burgess-Herbert SL, Paigen B et al. Effects of atherogenic diet on hepatic gene expression across mouse strains. Physiol Genomics 2009 Nov 6;39(3):172-82. PMID: 19671657

Data Source Acknowledgements:

Churchill GA, Paigen B, Shockley KR, Witmer D

	Service initiated June 15, 2001. Site by Xiaodong Zhou, Lei Yan, Ning Liu, Zachary Sloan, Rudi Alberts, Arthur Centeno, Jintao Wang, Lu Lu, Kenneth Manly, Robert W. Williams, and colleagues.
	GeneNetwork support from: The UT Center for Integrative and Translational Genomics NIAAA Integrative Neuroscience Initiative on Alcoholism (U01AA13499, U24AA13513, U01AA014425) NIDA, NIMH, and NIAAA (P20-DA 21131) NCI MMHCC (U01CA105417), NCRR BIRN, (U24 RR021760)