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Complex-trait genetics: emergence of multivariate strategies

Nature Reviews Neuroscience volume 3, pages 478–485 (2002)Cite this article

Abstract

Complex traits, including many disease-related traits, are influenced by multiple genes. Bivariate approaches that associate one gene with one trait are yielding to multivariate methods to synthesize the effects of multiple genes, integrate results across independent studies, and aid in the identification of coordinated pathways and interactions between loci.

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Acknowledgements

We are indebted to R. Hen for providing the breeding stocks of 5-HT1B mice. We are also grateful for the technical assistance of S. Burkhart-Kasch and A. Forster. We thank A. Palmer and J. Crabbe for insightful discussions. Our work is supported by grants from the Department of Veterans Affairs, the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse.

Author information

Authors and Affiliations

  1. the Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, and Research Service, Veterans Affairs Medical Center, Portland, 97201, Oregon, USA

    Tamara J. Phillips & John K. Belknap

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  1. Tamara J. Phillips
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Correspondence to Tamara J. Phillips.

Related links

Related links

DATABASES

LocusLink

Brn3a

Brn3b

Brn3c

Clock

CRFR1

CRFR2

Htr1b

Mvb1

Pitpn

Y1 receptor

Y2 receptor

Mouse Phenome Project

129

129S1/SvImJ

A/J

AKR/J

BALB/cByJ

BTBR/N

C3H/HeJ

C57BL/6J

DBA/2J

FVB/NJ

LP/J

NON/Lt

FURTHER INFORMATION

Encyclopedia of Life Sciences

quantitative genetics

Mouse Genome Informatics

Glossary

BAYESIAN APPROACH

A statistical method that allows the use of prior information to evaluate the posterior probabilities of different hypotheses.

BIDIRECTIONAL SELECTIVE BREEDING

A breeding strategy in which two opposite phenotypes (for example, high and low body weight) are identified in a population and selected over multiple generations.

CLUSTER ANALYSIS

An analytical tool for solving classification problems. The object is to sort items into groups such that the degree of association is strong between members of the same cluster and weak between members of different clusters.

CONGENIC STRAIN

A strain that is produced by a breeding strategy that delineates a genomic region containing a trait locus. 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.

CONSOMIC STRAIN

Also known as a chromosome-substitution strain, it 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.

DENDROGRAM

A branching diagram that represents a hierarchy of categories on the basis of degree of similarity or number of shared characteristics. The results of clustering can be presented as dendrograms in which the distance along the tree from one element to the next represents the relative degree of similarity.

EFFECT SIZE

A measure of effect that is adopted when different scales are used to measure an outcome. It is usually defined as the difference in means between the experimental and control groups, divided by the standard deviation of the control or both groups. As effect size is a standardized measure, it allows us to compare and/or combine the effects found in different studies of the same phenomenon.

EPISTASIS

Any genetic interaction in which the combined phenotypic effect of two or more loci is less than (negative epistasis) or greater than (positive epistasis) the sum of effects at individual loci.

INTERVAL MAPPING

A collection of methods for mapping quantitative trait loci. Simple interval mapping uses one or two pairs of flanking markers at a time, and assesses the probability that an interval between two markers is associated with a QTL. Composite interval mapping assesses the probability that an interval between two markers is associated with a QTL, while controlling for the effects of other markers on the trait of interest.

k-MEANS CLUSTER ANALYSIS

A class of cluster analysis in which items are sorted into a specific number of clusters (k) that show the greatest possible distinction.

MARKER GENOTYPING

The process of determining the genotype of a particular subject at a previously mapped marker locus.

MICROARRAY

A device that is used to interrogate complex nucleic-acid samples by hybridization. It makes it possible to count the number of different RNA or cDNA molecules that are present in a sample as a preparative stage for their subsequent characterization.

MICROSATELLITE

A class of repetitive DNA that is made up of repeats that are 2–8 nucleotides in length. They can be highly polymorphic and are frequently used as molecular markers in studies of population genetics.

MODIFIER GENE

A gene that influences the phenotypic expression of another gene.

MONTE CARLO SIMULATION

The use of randomly generated or sampled data and computer simulations to obtain approximate solutions to complex mathematical and statistical problems.

MULTIDIMENSIONAL SCALING

A method of analysis that provides a visual representation of the pattern of similarities between data sets. For example, given a matrix of similarities between various phenotypes, multidimensional scaling plots them on a map such that phenotypes that are perceived to be similar are placed near to each other and those that are perceived to be different are placed far apart.

PLEIOTROPY

The capacity of different alleles of a gene to affect more than one phenotype.

POLYMORPHISM

The simultaneous existence in the same population of two or more genotypes in frequencies that cannot be explained by recurrent mutations.

PRINCIPAL COMPONENTS ANALYSIS

A mathematical procedure that transforms a series of correlated variables into a smaller number of uncorrelated variables that are known as principal components. The first principal component accounts for as much of the variability in the data as possible. Subsequent principal components gradually account for the remaining variability.

QUANTITATIVE TRAIT LOCUS

A genetic locus or chromosomal region that contributes to variability in a complex quantitative trait (such as body weight), as identified by statistical analysis.

REALIZED HERITABILITY

Heritability measured by a response to phenotypic selection. If a phenotype is heritable and selected in two different populations, the two populations will diverge over time and the divergence can be quantified. Realized heritability is an estimate of what the heritability of the phenotype needs to be to account for the rate of divergence that is observed after selection.

RECOMBINANT INBRED STRAIN

A population of multiple strains of fully homozygous subjects that is obtained by repeated breeding from a second-generation hybrid of two inbred strains. The collection of strains comprises 50% of each parental genome in different combinations.

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Phillips, T., Belknap, J. Complex-trait genetics: emergence of multivariate strategies. Nat Rev Neurosci 3, 478–485 (2002). https://doi.org/10.1038/nrn847

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