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

Manenti, G; Galbiati, F; Giannì-Barrera, R; Pettinicchio, A; Acevedo, A; Dragani, TA

HERO ID

2216261

Reference Type

Journal Article

Year

2004

Language

English

PMID

15064703

HERO ID 2216261
In Press No
Year 2004
Title Haplotype sharing suggests that a genomic segment containing six genes accounts for the pulmonary adenoma susceptibility 1 (Pas1) locus activity in mice
Authors Manenti, G; Galbiati, F; Giannì-Barrera, R; Pettinicchio, A; Acevedo, A; Dragani, TA
Journal Oncogene
Volume 23
Issue 25
Page Numbers 4495-4504
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 amino-acid 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.
Doi 10.1038/sj.onc.1207584
Pmid 15064703
Wosid WOS:000221661300015
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English