Fine mapping of epistatic genetic determinants of blood pressure on rat chromosome 5

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Abstract

Background:

Previously, using linkage analysis and substitution mapping, two closely-linked interactive blood pressure quantitative trait loci (QTLs), BP QTL1 and BP QTL2, were located within a 13.96 Mb region from 117894038 to 131853815 bp (RGSC 3.4 version) on rat chromosome 5 (RNO5). This was done by using a series of congenic strains consisting of genomic segments of the Dahl salt-sensitive (S) rat substituted with that of the normotensive Lewis (LEW) rat. The interactive nature of the two loci was further confirmed by the construction and characterization of a panel of S.LEW bicongenic strains and corresponding S.LEW monocongenic strains, which provided definitive evidence of epistasis (genetic interaction) between BP QTL1 (7.77 Mb) and BP QTL2 (4.18 Mb). The purpose of this work was to further map these interacting QTLs.

Method:

A new panel of seven new S.LEW bicongenic strains was constructed and characterized for BP.

Results:

The data obtained from these new strains further resolved BP QTL1 from 7.77 to 2.93 Mb. Further, BP QTL2 was traceable as not being a single QTL, but a composite of at least three QTLs, LEW alleles at two of which located within 2.26 Mb and 175 kb lowered BP but the third one located within 1.31 Mb increased BP.

Conclusion:

Lack of coding variation within any of the regions further mapped within the previous QTL2 suggests noncoding variation as likely responsible for the observed epistasis.

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