HZI Lung M430v2 (Apr08) RMA

Summary

Phase I of BXD lung transcriptome mapping project. Project organized by Drs. Robert Williams, Klaus Schughart, Lu Lu. Started November 29, 2008. There are total 70 samples in phase I including 50 BXD strains and 10 paired inbred strains.

Respir Res. 2011 May 2;12:61. doi: 10.1186/1465-9921-12-61.

Genome-wide analysis of the mouse lung transcriptome reveals novel molecular gene interaction networks and cell-specific expression signatures.

Alberts R1, Lu L, Williams RW, Schughart K.

Author information

Erratum in

• Respir Res. 2012;13(1):5. 

Abstract

BACKGROUND: 

The lung is critical in surveillance and initial defense against pathogens. In humans, as in mice, individual genetic differences strongly modulate pulmonary responses to infectious agents, severity of lung disease, and potential allergic reactions. In a first step towards understanding genetic predisposition and pulmonary molecular networks that underlie individual differences in disease vulnerability, we performed a global analysis of normative lung gene expression levels in inbred mouse strains and a large family of BXD strains that are widely used for systems genetics. Our goal is to provide a key community resource on the genetics of the normative lungtranscriptome that can serve as a foundation for experimental analysis and allow predicting genetic predisposition and response to pathogens, allergens, and xenobiotics.

METHODS: 

Steady-state polyA+ mRNA levels were assayed across a diverse and fully genotyped panel of 57 isogenic strains using the Affymetrix M430 2.0 array. Correlations of expression levels between genes were determined. Global expression QTL (eQTL) analysis and network covariance analysis was performed using tools and resources in GeneNetwork http://www.genenetwork.org.

RESULTS: 

Expression values were highly variable across strains and in many cases exhibited a high heritability factor. Several genes which showed a restricted expression to lung tissue were identified. Using correlations between gene expression values across all strains, we defined and extended memberships of several important molecular networks in the lung. Furthermore, we were able to extract signatures of immune cell subpopulations and characterize co-variation and shared genetic modulation. Known QTL regions for respiratory infection susceptibility were investigated and several cis-eQTL genes were identified. Numerous cis- and trans-regulated transcripts and chromosomal intervals with strong regulatory activity were mapped. The Cyp1a1 P450 transcript had a strong trans-acting eQTL (LOD 11.8) on Chr 12 at 36 ± 1 Mb. This interval contains the transcription factor Ahr that has a critical mis-sense allele in the DBA/2J haplotype and evidently modulates transcriptional activation by AhR.

CONCLUSIONS: 

Large-scale gene expression analyses in genetic reference populations revealed lung-specific and immune-cell gene expression profiles and suggested specific gene regulatory interactions.

PMID:21535883 PMCID:PMC3105947 DOI:10.1186/1465-9921-12-61

About cases

Index Array Sample Strain Sex Age Color Pool Size Source 1 R4435LU.CEL R4435LU BXD100 F 64 black 2 UTM RW 2 R4436LU.CEL R4436LU BXD14 F 85 black 2 UTM RW 3 R4437LU.CEL R4437LU BXD34 F 58 black 5 UTM RW 4 R4438LU.CEL R4438LU BXD39 F 63 gray 3 UTM RW 5 R4439LU.CEL R4439LU BXD40 F 54 gray 3 ORNL 6 R4440LU.CEL R4440LU BXD45 F 60 dilute brown DBA 4 UTM RW 7 R4441LU.CEL R4441LU BXD50 F 64 dilute brown DBA 4 ORNL 8 R4442LU.CEL R4442LU BXD1 F 88 dilute brown DBA 3 UTM RW 9 R4443LU.CEL R4443LU BXD16 F 79 gray 3 ORNL 10 R4444LU.CEL R4444LU BXD12 F 61 gray 5 UTM RW 11 R4445LU.CEL R4445LU BXD21 F 50 dilute brown DBA 3 ORNL 12 R4446LU.CEL R4446LU BXD19 F 49 gray 3 ORNL 13 R4447LU.CEL R4447LU BXD27 F 85 brown 3 UTM RW 14 R4448LU.CEL R4448LU BXD31 F 81 black 3 UTM RW 15 R4449LU.CEL R4449LU BXD32 F 68 black 5 ORNL 16 R4450LU.CEL R4450LU BXD33 F 61 gray 2 ORNL 17 R4451LU.CEL R4451LU BXD42 F 65 black 2 UTM RW 18 R4452LU.CEL R4452LU BXD43 F 79 black 2 UTM RW 19 R4453LU.CEL R4453LU BXD45 F 60 dilute brown DBA 4 UTM RW 20 R4454LU.CEL R4454LU BXD55 M 80 brown 3 UTM RW 21 R4455LU.CEL R4455LU BXD56 M 91 black 3 UTM RW 22 R4456LU.CEL R4456LU BXD66 F 80 brown 3 UTM RW 23 R4457LU.CEL R4457LU BXD68 F 65 brown 4 UTM RW 24 R4459LU-re.CEL R4459LU BXD89 F 79 dilute brown DBA 2 UTM RW 25 R4460LU.CEL R4460LU BXD51 M 81 black 2 UTM RW 26 R4461LU.CEL R4461LU BXD97 F N/A N/A N/A N/A 27 R4462LU.CEL R4462LU BXD48 F 61 black 3 ORNL 28 R4463LU.CEL R4463LU BXD60 M 93 brown 2 UTM RW 29 R4464LU.CEL R4464LU BXD62 M 80 brown 2 UTM RW 30 R4465LU.CEL R4465LU BXD69 M 63 dilute brown DBA 5 UTM RW 31 R4466LU.CEL R4466LU BXD70 M 75 dilute brown DBA 3 UTM RW 32 R4467LU.CEL R4467LU BXD71 M 64 dilute brown DBA 4 UTM RW 33 R4468LU.CEL R4468LU BXD73 M 59 dilute brown DBA 3 UTM RW 34 R4469L.CEL R4469LU BXD75 M 51 dilute brown DBA 4 UTM RW 35 R4470L.CEL R4470LU BXD2 M 84 black 3 UTM RW 36 R4471H-re.CEL R4471LU BXD83 M 75 dilute brown DBA 2 UTM RW 37 R4472L.CEL R4472LU BXD84 M 78 dilute brown DBA 2 UTM RW 38 R4473LU.CEL R4473LU BXD86 M 77 black 3 UTM RW 39 R4474LU.CEL R4474LU BXD87 M 67 black 3 UTM RW 40 R4475LU.CEL R4475LU BXD9 M 78 dilute brown DBA 3 UTM RW 41 R4476LU.CEL R4476LU BXD90 M 63 dilute brown DBA 3 UTM RW 42 R4477LU.CEL R4477LU BXD65 M 59 brown 3 ORNL 43 R4478LU.CEL R4478LU BXD6 M 92 gray 3 UTM RW 44 R4479LU.CEL R4479LU BXD96 M 71 black 3 UTM RW 45 R4480LU.CEL R4480LU BXD97 M 80 brown 3 UTM RW 46 R4481LU.CEL R4481LU BXD98 M 80 dilute brown DBA 2 UTM RW 47 R4482LU.CEL R4482LU BXD99 M 72 dilute brown DBA 2 UTM RW 48 R4483LU.CEL R4483LU BXD22 M 66 gray 2 UTM RW 49 R4484LU.CEL R4484LU BXD25 M 54 brown 3 UTM RW 50 R4485LU.CEL R4485LU B6D2F1 M 62 black 5 UTM RW 51 R4486LU.CEL R4486LU B6D2F1 F 70 black 2 UTM RW 52 R4487LU.CEL R4487LU BALB/cByJ F 91 white 3 UTM RW 53 R4488LU.CEL R4488LU BALB/cByJ M 91 white 2 UTM RW 54 R4489LU.CEL R4489LU D2B6F1 F 61 black 2 UTM RW 55 R4490LU.CEL R4490LU D2B6F1 M 61 black 3 UTM RW 56 R4491LU.CEL R4491LU FVB/NJ F 62 white 5 UTM RW 57 R4492LU.CEL R4492LU FVB/NJ M 73 white 3 UTM RW 58 R4493LU.CEL R4493LU WSB/EiJ F 76 agouti 3 UTM RW 59 R4494LU.CEL R4494LU WSB/EiJ M 76 agouti 3 UTM RW 60 R4495LU.CEL R4495LU C57BL/6J F 65 black 3 UTM RW 61 R4496LU.CEL R4496LU C57BL/6J M 65 black 2 UTM RW 62 R4497LU.CEL R4497LU 129X1/SvJ F 65 white 4 JAX 63 R4498LU.CEL R4498LU 129X1/SvJ M 66 white 4 JAX 64 R4499LU.CEL R4499LU DBA/2J F 65 dilute brown DBA 3 ORNL 65 R4500LU.CEL R4500LU DBA/2J M 59 dilute brown DBA 2 JAX 66 R4501LU.CEL R4501LU LP/J F 65 agouti 4 JAX 67 R4502LU.CEL R4502LU LP/J M 65 agouti 4 JAX 68 R4503LU.CEL R4503LU SJL/J F 63 white 4 JAX 69 R4504LU.CEL R4504LU SJL/J M 65 white 4 JAX