, Volume 26, Issue 2, pp 135-143
Date: 18 Feb 2010

Quantitative genetics: past and present

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Abstract

Most characters of economic importance in plants and animals, and complex diseases in humans, exhibit quantitative variation, the genetics of which has been a fascinating subject of study since Mendel’s discovery of the laws of inheritance. The classical genetic basis of continuous variation based on the infinitesimal model of Fisher and mostly using statistical methods has since undergone major modifications. The advent of molecular markers and their extensive mapping in several species has enabled detection of genes of metric characters known as quantitative trait loci (QTL). Modeling the high-resolution mapping of QTL by association analysis at the population level as well as at the family level has indicated that incorporation of a haplotype of a pair of single-nucleotide polymorphisms (SNPs) in the model is statistically more powerful than a single marker approach. High-throughput genotyping technology coupled with micro-arrays has allowed expression of thousand of genes with known positions in the genome and has provided an intermediate step with mRNA abundance as a sub-phenotype in the mapping of genotype onto phenotype for quantitative traits. Such gene expression profiling has been combined with linkage analysis in what is known as eQTL mapping. The first study of this kind was on budding yeast. The associated genetic basis of protein abundance using mass spectrometry has also been attempted in the same population of yeast. A comparative picture of transcript vs. protein abundance levels indicates that functionally important changes in the levels of the former are not necessarily reflected in changes in the levels of the latter. Genes and proteins must therefore be considered simultaneously to unravel the complex molecular circuitry that operates within a cell. One has to take a global perspective on life processes instead of individual components of the system. The network approach connecting data on genes, transcripts, proteins, metabolites etc. indicates the emergence of a systems quantitative genetics. It seems that the interplay of the genotype-phenotype relationship for quantitative variation is not only complex but also requires a dialectical approach for its understanding in which ‘parts’ and ‘whole’ evolve as a consequence of their relationship and the relationship itself evolves.