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Multifactorial genetics

Rat genetics: attachign physiology and pharmacology to the genome

Nature Reviews Genetics volume 3, pages 33–42 (2002)Cite this article

Key Points

  • The rat is an important model organism for systems biology research, as it has a wealth of physiological and pharmacological data to offer, and more than 200 inbred models of human complex disease.

  • The Rat Genome Project is providing biologists with a powerful set of tools with which to develop better models of human disease at the phenotypic and genomic level.

  • The rat genome can be annotated with biological functions that can relate to complex disease. Methods for doing this range from quantitative trait loci mapping in inbred rat strains to developing and studying congenic, consomic and transgenic rat strains to facilitate gene discovery and a better understanding of the genes that underlie complex disease.

  • Comparative genomics allows different types of information that have been derived from various model organisms to be integrated to generate a synergistic platform for understanding complex disease mechanisms.

Abstract

During the past five years, the Rat Genome Project has been rapidly gaining momentum, especially since the announcement in August 2000 of plans to sequence the rat genome. Combined with the wealth of physiological and pharmacological data for the rat, the genome sequence should facilitate the discovery of mammalian genes that underlie the physiological pathways that are involved in disease. Most importantly, this combined physiological and genomic information should also lead to the development of better pre-clinical models of human disease, which will aid in the development of new therapeutics.

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Figure 1: Integrating data from the rat and mouse for studies of human disease.
Figure 2: Functional complementation by transgenesis.
Figure 3: QTL associated with complex disease phenotypes that map to regions of conserved synteny in the human, rat and mouse genomes.

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Acknowledgements

H.J.J. and A.E.K. are supported by grants from the National Institutes of Health.

Author information

Authors and Affiliations

  1. Department of Physiology, Human and Molecular Genetics Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, 53226, Wisconsin, USA

    Howard J. Jacob & Anne E. Kwitek

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  1. Howard J. Jacob
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  2. Anne E. Kwitek
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Correspondence to Howard J. Jacob.

Related links

Related links

DATABASES

LocusLink 

Ace

ACE

ADRA2A

Afw3

AGT

Aid

APOA4

BBS1

Bhr2

Cd36

Eae3

Fob2

GYS1

GCK

Hlq5

Idd6

IDDM2

IGF1

INSR

Lbw4

LDLR

LIPE

NPY

PRKWNK4

RA

UCP2 

OMIM 

Crohn disease

pseudohypoaldosteronism type II

type II (non-insulin-dependent) diabetes

FURTHER INFORMATION

Baylor College of Medicine ENU mutagenesis screen

GSF ENU Mouse Mutagenesis Project

Harwell ENU mutagenesis programme

McLaughlin Research Institute ENU mutagenesis screen

Medical College of Wisconsin

PubMed

QTL maps and physiological profiles

Rattus norvegicus

Strain query form at Rat Genome Database

The Jackson Laboratory

The PhysGen Project

US National Heart, Lung, and Blood Institute — Programs for Genome Applications

Virtual comparative maps at the Rat Genome Database

Glossary

INBRED STRAIN

A strain that is generated through systematic inbreeding, which fixes certain alleles in a strain so that they replace all other alleles that were present in an outbred population.

QUANTITATIVE TRAIT LOCUS

(QTL). A genetic locus that is identified through the statistical analysis of complex traits (such as height or body weight). These traits are typically affected by more than one gene and also by the environment.

CONGENIC

A strain that is produced by a breeding strategy in which recombinants between two inbred strains are backcrossed to produce a strain that carries a single segment from one strain on the genetic background of the other. The selected segment can contain a quantitative trait locus.

CONSOMIC

A strain that is produced by a breeding strategy in which recombinants between two inbred strains are backcrossed to produce a strain that carries a single chromosome from one strain on the genetic background of the other.

SYSTEMS BIOLOGY

The investigation of all of the elements of a particular biological system, rather than of individual genes or proteins. Systems biology aims to investigate the behaviour and relationships of all of the elements in a particular biological system.

MARKER-ASSISTED SELECTION

The use of genetic markers to predict the inheritance of alleles at a closely linked trait locus.

INTROGRESSION

Transfer of genetic material from one strain to another by repeated backcrosses.

COMPLEMENTATION TEST

A breeding strategy to test whether two mutations are non-allelic when combined in an organism. If the resulting phenotype is wild type, the mutations are non-allelic and said to complement each other.

QUANTITATIVE COMPLEMENTATION

A breeding strategy to identify genes that contribute to a quantitative trait locus (QTL). A QTL allele is crossed to animals that carry null mutations at each candidate gene in the QTL. If the phenotypic effect of the QTL allele on the progeny is not the same in mutant and wild-type backgrounds, allelism (quantitative non-complementation) between the mutant gene and the gene in the QTL is indicated.

ORTHOLOGOUS GENE

Homologous gene in different species, the lineage of which derives from a common ancestral gene without gene duplication or horizontal transmission.

BARORECEPTOR REFLEX

A reflex with a negative-feedback loop system; as blood pressure increases or decreases, the baroreceptor detects the event and initiates a cascade of physiological mechanisms that results in a return to baseline blood pressure.

LINKAGE DISEQUILIBRIUM

The condition in which the frequency of a particular haplotype for two loci is significantly greater or less than that expected from the product of the observed allelic frequencies at each locus.

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Jacob, H., Kwitek, A. Rat genetics: attachign physiology and pharmacology to the genome. Nat Rev Genet 3, 33–42 (2002). https://doi.org/10.1038/nrg702

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