Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics.

Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics. Research Abstract Details 

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Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics. Abstract Text:

Haijin Meng,Iset Vera,Nam Che,Xuping Wang,Susanna S Wang,Leslie Ingram-Drake,Eric E Schadt,Thomas A Drake,Aldons J Lusis,

The genetic factors contributing to the complex disorder of myocardial calcification are largely unknown. Using a mouse model, we fine-mapped the major locus (Dyscalc1) contributing to the dystrophic cardiac calcification (DCC) to an 840-kb interval containing 38 genes. We then identified the causal gene by using an approach integrating genetic segregation and expression array analyses to identify, on a global scale, cis-acting DNA variations that perturb gene expression. By studying two intercrosses, in which the DCC trait segregates, a single candidate gene (encoding the ATP-binding cassette transporter ABCC6) was identified. Transgenic complementation confirmed Abcc6 as the underlying causal gene for Dyscalc1. We demonstrate that in the cross, the expression of Abcc6 is highly correlated with the local mineralization regulatory system and the BMP2-Wnt signaling pathway known to be involved in the systemic regulation of calcification, suggesting potential pathways for the action of Abcc6 in DCC. Our results demonstrate the power of the integrative genomics in discovering causal genes and pathways underlying complex traits.

Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics. Publishing Authors By Initials

H Meng,I Vera,N Che,X Wang,SS Wang,L Ingram-Drake,EE Schadt,TA Drake,AJ Lusis,

For similar peptides: intercellular signaling peptides and proteins: wnt proteins research abstracts see: peptides: intercellular signaling peptides and proteins: wnt proteins research

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Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 4530-5

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 6

MONTH: 03

YEAR: 2007

Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics. Keywords Mesh Terms:

KEYWORDS: Wnt Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics. Information

Substance Name: Osteopontin

Registry Number: 106441-73-0

Grant and Affiliation Information for Identification of Abcc6 as the major causal gene for dystrophic cardiac calcification in mice through integrative genomics.

AFFILIATION: Department of Medicine, Cardiology Division, University of California-Los Angeles, Los Angeles, CA 90095, USA. hmeng@mednet.ucla.edu

Country: United States

AGENCY: United States NHLBI

GRANT: P01 HL 30568

ACRONYM: HL

MEDLINETA: Proc Natl Acad Sci U S A

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