Comparative sequence analysis in eight inbred strains of the metastasis modifier QTL candidate gene Brms1

Park, Yeong-Gwan; Lukes, Luanne; Yang, Howard H.; Debies, Michael T.; Samant, Rajeev S.; Welch, Danny R.; Lee, Maxwell; Hunter, Kent W.

doi:10.1007/s00335-001-2151-6

Cited by 14 publications

(5 citation statements)

References 8 publications

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“…C57BR/cdJ and C57BL/6J are closely related in genome-wide scans, but these two strains are distinct in the distal Chr 7 region and C57BR/cdJ and SM/J are entirely identical. These results are consistent with previous observations that local and global hereditary relationships often differ (Frazer et al 2004 ; Park et al 2002 ).…”

Section: Resultssupporting

confidence: 93%

Ancestral bias in the Hras1 gene and distal Chromosome 7 among inbred mice

2007

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Inbred strains of mice vary in their frequency of liver tumors initiated by a mutation in the Hras1 (H-ras) proto-oncogene. We sequenced 4.5 kb of the Hras1 gene on distal Chr 7 in a diverse set of 12 commonly used laboratory inbred strains of mice and detected no sequence variation to account for strain-specific differences in Hras1 mutation prevalence. Furthermore, the Hras1 sequence is essentially monoallelic for an ancestral gene derived from the M. m. domesticus species. To determine if the monoallelism and associated low rate of polymorphism are unique to Hras1 or representative of the general chromosomal locale, we extended the sequence analysis to 12 genes in the final 8 Mb of distal Chr 7. A region of at least 2.5 Mb that encompasses several genes, including Hras1 and the H19/Igf2 loci, demonstrates virtually no sequence variation. The 12 inbred strains share one dominant haplotype derived from the M. m. domesticus allele. Chromosomal regions flanking the monoallelic segment exhibit a significantly higher rate of variation and multiple haplotypes, a majority of which are attributed to M. m. domesticus or M. m. musculus ancestry.

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Section: Resultssupporting

confidence: 93%

Ancestral bias in the Hras1 gene and distal Chromosome 7 among inbred mice

2007

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“…We also cannot rule out the possibility that Skts5 may have unique genomic properties compared to other loci. Previous studies have reported different phylogenetic trees when comparing sequence samples from across the genome (global comparison) with gene-specific phylogenetic trees (local comparison)[ 39 ]. Skts5 may represent a region with unique local characteristics between M. spretus strains.…”

Section: Discussionmentioning

confidence: 99%

Sequence divergence of Mus spretus and Mus musculus across a skin cancer susceptibility locus

et al. 2008

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Background: Mus spretus diverged from Mus musculus over one million years ago. These mice are genetically and phenotypically divergent. Despite the value of utilizing M. musculus and M. spretus for quantitative trait locus (QTL) mapping, relatively little genomic information on M. spretus exists, and most of the available sequence and polymorphic data is for one strain of M. spretus, Spret/Ei. In previous work, we mapped fifteen loci for skin cancer susceptibility using four different M. spretus by M. musculus F1 backcrosses. One locus, skin tumor susceptibility 5 (Skts5) on chromosome 12, shows strong linkage in one cross.

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“…Hunter and colleagues were first to show metastatic susceptibility loci in a genetic screen crossing MMTV – polyoma middle T mice (FVB/N-Tg(MMTV-PyVT)634Mul/J, hereafter PyMT) on the FVB/NJ genetic background with different mice strains resulting in F 1 progeny with different primary tumor latencies and metastatic potentials (8, 10, 11). Tumors from the PyMT model progress through stages that are comparable to human breast cancer, and biomarker expression in PyMT tumors is similarly consistent with those associated with poor outcome in human disease (12, 13).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Genetics Regulate Breast Cancer Tumorigenicity and Metastatic Potential

et al. 2015

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Current paradigms of carcinogenic risk suggest that genetic, hormonal, and environmental factors influence an individual’s predilection for developing metastatic breast cancer. Investigations of tumor latency and metastasis in mice have illustrated differences between inbred strains, but the possibility that mitochondrial genetic inheritance may contribute to such differences in vivo has not been directly tested. In this study, we tested this hypothesis in mitochondrial-nuclear exchange (MNX) mice we generated, where cohorts shared identical nuclear backgrounds but different mtDNA genomes on the background of the PyMT transgenic mouse model of spontaneous mammary carcinoma. In this setting, we found that primary tumor latency and metastasis segregated with mtDNA, suggesting that mtDNA influences disease progression to a far greater extent than previously appreciated. Our findings prompt further investigation into metabolic differences controlled by mitochondrial process as a basis for understanding tumor development and metastasis in individual subjects.

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Comparative sequence analysis in eight inbred strains of the metastasis modifier QTL candidate gene Brms1

Cited by 14 publications

References 8 publications

Ancestral bias in the Hras1 gene and distal Chromosome 7 among inbred mice

Ancestral bias in the Hras1 gene and distal Chromosome 7 among inbred mice

Sequence divergence of Mus spretus and Mus musculus across a skin cancer susceptibility locus

Mitochondrial Genetics Regulate Breast Cancer Tumorigenicity and Metastatic Potential

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