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Testicular germ cell tumor susceptibility genes from the consomic 129.MOLF-Chr19 mouse strain

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Abstract

Chromosome substitution strains (CSS or consomic strains) are useful for mapping phenotypes to chromosomes. However, huge efforts are needed to identify the gene(s) responsible for the phenotype in the complex context of the chromosome. Here we report the identification of candidate disease genes from a CSS by using a combination of genetic and genomic approaches and by using knowledge about the germ cell tumor disease etiology. We used the CSS 129.MOLF-Chr19 chromosome substitution strain, in which males develop germ cell tumors of the testes at an extremely high rate. We were able to identify three protein-coding genes and one microRNA on chromosome 19 that have previously not been implicated to be testicular tumor susceptibility genes. Our findings suggest that changes in gene expression levels in the gonadal tissues of multiple genes from Chr 19 likely contribute to the high testicular germ cell tumor (TGCT) incidence of the 129.MOLF-Chr19 strain. Our data advance the use of CSS to identify disease susceptibility genes and demonstrate that the 129.MOLF-Chr19 strain serves as a useful model to elucidate the genetics and biology of germ cell transformation and tumor development.

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Abbreviations

SNP:

single nucleotide polymorphism

nt:

nucleotide

qRT-PCR:

quantitative real-time polymerase chain reaction

Chr:

chromosome

TGCT:

testicular germ cell tumor

PN1:

postnatal day 1

E:

embryonic day

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Acknowledgments

The authors thank Henry Adams and microarray core facility personnel at the M.D. Anderson Cancer Center (Cancer Center Support Grant CA #16672) for invaluable technical support. This work was supported by National Cancer Institute grant CA093754 and David Carmine Cancer Research Fund to AM.

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Authors and Affiliations

  1. Department of Cancer Genetics, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1006, Houston, Texas, 77030, USA

    Rui Zhu & Angabin Matin

  2. Department of Bioinformatics and Computational Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, USA

    Yuan Ji

  3. Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, 77030, USA

    Lianchun Xiao

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  1. Rui Zhu
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  3. Lianchun Xiao
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  4. Angabin Matin
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Correspondence to Angabin Matin.

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Zhu, R., Ji, Y., Xiao, L. et al. Testicular germ cell tumor susceptibility genes from the consomic 129.MOLF-Chr19 mouse strain. Mamm Genome 18, 584–595 (2007). https://doi.org/10.1007/s00335-007-9036-2

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  • DOI: https://doi.org/10.1007/s00335-007-9036-2

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