Molecular Genetic Analysis of the Melanoma Regulatory Locus in Xiphophorus Interspecies Hybrids

Simple item page
dc.contributor.authorLu, Yuan
dc.contributor.authorBoswell, Mikki
dc.contributor.authorBoswell, William T.
dc.contributor.authorKneitz, Susanne
dc.contributor.authorHausmann, Michael
dc.contributor.authorKlotz, Barbara
dc.contributor.authorRegneri, Janine
dc.contributor.authorSavage, Markita G.
dc.contributor.authorAmores, Angel
dc.contributor.authorPostlethwait, John
dc.contributor.authorWarren, Wesley C.
dc.contributor.authorSchartl, Manfred
dc.contributor.authorWalter, Ronald B.
dc.date.accessioned2020-04-02T20:09:54Z
dc.date.available2020-04-02T20:09:54Z
dc.date.issued2017-08
dc.description.abstractDevelopment of spontaneous melanoma in Xiphophorus interspecies backcross hybrid progeny, (X. hellerii × [X. maculatus Jp 163 A × X. hellerii]) is due to Mendelian segregation of a oncogene (xmrk) and a molecularly uncharacterized locus, called R(Diff), on LG5. R(Diff) is thought to suppresses the activity of xmrk in healthy X. maculatus Jp 163 A parental species that rarely develop melanoma. To better understand the molecular genetics of R(Diff), we utilized RNA-Seq to study allele-specific gene expression of spontaneous melanoma tumors and corresponding normal skin samples derived from 15 first generation backcross (BC1) hybrids and 13 fifth generation (BC5) hybrids. Allele-specific expression was determined for all genes and assigned to parental allele inheritance for each backcross hybrid individual. Results showed that genes residing in a 5.81 Mbp region on LG5 were exclusively expressed from the X. hellerii alleles in tumor-bearing BC1 hybrids. This observation indicates this region is consistently homozygous for X. hellerii alleles in tumor bearing animals, and therefore defines this region to be the R(Diff) locus. The R(Diff) locus harbors 164 gene models and includes the previously characterized R(Diff) candidate, cdkn2x. Twenty-one genes in the R(Diff) region show differential expression in the tumor samples compared to normal skin tissue. These results further characterize the R(Diff) locus and suggest tumor suppression may require a multigenic region rather than a single gene variant. Differences in gene expression between tumor and normal skin tissue in this region may indicate interactions among several genes are required for backcross hybrid melanoma development.
dc.description.departmentChemistry and Biochemistry
dc.description.versionThis is the accepted manuscript version of an article published in Molecular Carcinogens.
dc.formatText
dc.format.extent19 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationLu, Y., Boswell, M., Boswell, W., Kneitz, S., Hausmann, M., Klotz, B., Regneri, J., Savage, M., Amores, A., Postlethwait, J., Warren, W., Schartl, M., & Walter, R. (2017). Molecular genetic analysis of the melanoma regulatory locus in Xiphophorus interspecies hybrids. Molecular Carcinogenesis, 56(8), pp. 1935–1944.
dc.identifier.doihttps://doi.org/10.1002/mc.22651
dc.identifier.issn1098-2744
dc.identifier.urihttps://hdl.handle.net/10877/9574
dc.language.isoen
dc.publisherJohn Wiley & Sons Ltd.
dc.sourceMolecular Carcinogenesis, 2017, Vol. 56, No. 8, pp. 1935–1944.
dc.subjectGordon-Kosswig model
dc.subjectinterspecies hybrids
dc.subjectallele specific gene expression
dc.subjectgenetic interaction
dc.subjectbioinformatics
dc.subjectChemistry and Biochemistry
dc.titleMolecular Genetic Analysis of the Melanoma Regulatory Locus in Xiphophorus Interspecies Hybrids
dc.typeArticle

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
nihms932331.pdf
Size:
797.94 KB
Format:
Adobe Portable Document Format
Description:
Download

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.54 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

College of Science and Engineering