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Epistasis

Epistasis

In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...

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Dissecting Epistatic QTL for Blood Pressure in Rats: Congenic Strains versus Heterogeneous Stocks, a Reality Check.

John P Rapp¹, Bina Joe¹

¹Physiological Genomics Laboratory, Department of Physiology and Pharmacology, Center for Hypertension and Precision Medicine, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.

Comprehensive Physiology

|November 6, 2019

Summary

Genetic interactions significantly influence blood pressure (BP) regulation. Understanding these complex genetic factors in models like the Dahl rat is crucial for hypertension research.

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Area of Science:

Genetics
Physiology
Molecular Biology

Background:

Advances in molecular genetics enable detailed study of quantitative traits like blood pressure (BP).
Hypertension is a complex trait influenced by multiple genetic factors.
The Dahl salt-sensitive (S) rat is a valuable model for studying genetic hypertension.

Purpose of the Study:

To review analytical techniques and findings for identifying genetic elements controlling BP.
To highlight the role of genetic interactions (epistasis) in BP regulation.
To compare classic and novel approaches for dissecting complex genetic traits.

Main Methods:

Interval mapping and substitution mapping using congenic strains in Dahl S rats.
Sophisticated statistical analysis on segregating or outbred model-organism populations.
Detailed examination of three chromosomal regions with varying genetic complexity influencing BP.

Main Results:

Genetic interactions (epistasis) are critical for BP regulation at multiple structural levels.
Specific DNA structural variations linked to biochemical and physiological mechanisms were identified in two cases.
Newer statistical methods demonstrate the existence of higher-order genetic interactions.

Conclusions:

Hypertension may be an outlier quantitative phenotype dependent on higher-order genetic interactions.
Identifying genetic elements and mechanisms for complex traits requires significant resources.
Classic and modern genetic mapping techniques are essential for understanding BP regulation.