IDENTIFICATION AND STRUCTURAL AND FUNCTIONAL ANALYSIS OF CANDIDATE GENES OF CHROMO...
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Identification and structural and functional analysis of candidate genes on chromosome 4 in SHR that may influence essential hypertension
Full text
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| Author(s): |
Samantha Kuwada Teixeira
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2013-12-10 |
| Examining board members: |
Jose Eduardo Krieger
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| Advisor: | Jose Eduardo Krieger |
| Abstract | |
Total genome scan in genetic models of complex diseases have been instrumental to select candidate genes underlying complex traits. We previously mapped 5 blood pressure related quantitative trait loci (BP-QTLs) that explain about 43% of the BP variance in a progeny derived from Spontaneous Hypertensive Rat (SHR) and Brown Norway (BN) rats. The BP-QTLs were then validated by derivation of congenic strains, including one for chromosome 4 (SHR.BN4) in which a segment from BN replaced the SHR sequences reducing basal systolic BP (~14 mm Hg). The aim of this project is to identify the candidate genetic variants within the chromosome interval based on differences in renal gene expression patterns and structural changes in both non-synonymous missense or within adjacent regulatory sequences that may contribute to hypertension. We identified 533 genes with renal expression, out of 682 in the interval, in which 28 presented differences in expression pattern in adult samples (congenic vs. SHR) and six presented non-synonymous missense alterations. In addition, 11 out of 28 differentially expressed genes showed structural alterations in adjacent conserved regions that potentially contribute to gene regulation. Taken together, using the proposed combination of strategies, we selected 34 hypertensive candidate genes in chromosome 4, in which 17 will be prioritized, to be further explored to assess their contribution to hypertension in the SHR and to essential hypertension in humans (AU) | |
| FAPESP's process: | 10/12871-8 - IDENTIFICATION AND STRUCTURAL AND FUNCTIONAL ANALYSIS OF CANDIDATE GENES OF CHROMOSOME 4 OF RATS SHR THAT COULD INFLUENCE ARTERIAL HYPERTENSION |
| Grantee: | Samantha Kuwada Teixeira |
| Support Opportunities: | Scholarships in Brazil - Master |