Haplotype sharing suggests that a genomic segment containing six genes accounts for the pulmonary adenoma susceptibility 1 (Pas1) locus activity in mice

Giacomo Manenti, Federica Galbiati, Roberto Giannì-Barrera, Angela Pettinicchio, Abraham Acevedo, Tommaso A. Dragani

Research output: Contribution to journalArticlepeer-review

Abstract

The pulmonary adenoma susceptibility 1 (Pas1) locus affects inherited predisposition and resistance to chemically induced lung tumorigenesis in mice. The A/J and C57BL/6J mouse strains carry the susceptibility and resistance allele, respectively. We identified and genotyped 65 polymorphisms in the Pas1 locus region in 29 mouse inbred strains, and delimited the Pas1 locus to a minimal region of 468 kb containing six genes. That region defined a core Pas1 haplotype with 42 tightly linked markers, including intragenic polymorphisms in five genes (Bcat1, Lrmp, Las1, Ghiso, and Kras2) and aminoacid changes in three genes (Lrmp, Las1, Lmna-rs1). In (A/J x C57BL/6J)F1 mouse lung tumors, the Lmna-rs1 gene was completely downregulated, whereas allele-specific downregulation of the C57BL/6J-derived allele was observed at the Las1 gene, suggesting the potential role of these genes in tumor suppression. These results indicate a complex multigenic nature of the Pas1 locus, and point to a functional role for both intronic and exonic polymorphisms of the six genes of the Pas1 haplotype in lung tumor susceptibility.

Original languageEnglish
Pages (from-to)4495-4504
Number of pages10
JournalOncogene
Volume23
Issue number25
DOIs
Publication statusPublished - May 27 2004

Keywords

  • Genetic susceptibility
  • Inbred strains
  • Kras2
  • Lung tumors

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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