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Fine mapping and candidate gene analysis of murine lung tumor susceptibility genes

Wang, Min
http://rave.ohiolink.edu/etdc/view?acc_num=osu1054682174

Abstract Details

2003, Doctor of Philosophy, Ohio State University, Medical Science.
We have utilized a newly developed F11 generation of Advanced Intercross Line (AIL) mouse population to fine map three mouse Pulmonary adenoma susceptibility (Pas) loci: Pas1 (on chromosome 6), Pas2 (on chromosome 17) and Pas3 (on chromosome 19). By selectively genotyping 30% of the population, we have confirmed the Pas1 QTL and refined it into an interval of approximately 1.0 cM (~1.3 Mb) in the vicinity of the Kras2 gene. The Pas2 QTL was detected by both ANOVA and regression analysis but not by Mapmaker software. An interaction between the Pas1 and Pas2 QTLs was also revealed. However, the Pas3 QTL has not been confirmed in this study. On the other hand, congenic strategy was also utilized to fine map the Pas1 locus. A set of new polymorphic markers has been developed to assist this fine-structure mapping. Combining results from the AIL project and the congenic project, we have refined the Pas1 QTL into a less than 1-Mb minimum candidate region based on the Celera mouse genome map encompassed by the markers D6Osu6 and D6Osu11. There are 24 putative genes located within this region. Candidate gene screening for this region has presented the Lrmp/Jaw1, Ak016641/Pas1c1 (for Pas1 candidate 1) and a novel gene, Pas1c2 (for Pas1 candidate 2) as strong candidates for the Pas1 QTL, and they will be further tested by in vitro and in vivo functional analyses. Using a similar congenic strategy, the Pulmonary adenoma resistance 2 (Par2) QTL has been narrowed to an approximately 6.3-Mb region flanked by the marker D18Mit103 and the marker D18Mit162. Four genes are possible Par2 candidates based on real-time PCR analyses, including Myo5b, Smad7, Mapk4, and GABA-A receptor-like gene mCG58197. Sequencing analyses for this region found that the Rad30b gene, encoding the DNA–dependent polymerase iota (Polé), carries 25 nucleotide polymorphisms in its coding region between the A/J and BALB/c strains, leading to ten amino-acid alterations. Functional analyses on the above five genes will be needed to clarify their Par2 candidacy. In addition, computational Single Nucleotide Polymorphism (SNP) analyses revealed that 54 putative genes carried various types of SNPs when comparing genomic sequences from A/J, 129X1/svJ, 129S1/svImJ, DBA/2J, and C57BL/6J mice. Screening of these SNPs in the future may help us find new polymorphic markers and identify new Par2 candidate genes.
Ming You (Advisor)
Christoph Plass (Advisor)
Gary Stoner (Other)
Yian Wang (Other)
lung tumor; mouse; susceptibility

Recommended Citations

Citations

  • Wang, M. (2003). Fine mapping and candidate gene analysis of murine lung tumor susceptibility genes [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1054682174

    APA Style (7th edition)

  • Wang, Min. Fine mapping and candidate gene analysis of murine lung tumor susceptibility genes. 2003. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1054682174.

    MLA Style (8th edition)

  • Wang, Min. "Fine mapping and candidate gene analysis of murine lung tumor susceptibility genes." Doctoral dissertation, Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1054682174

    Chicago Manual of Style (17th edition)

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© 2003, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.