Welcome to the 
Mackay Lab

The genetic basis of quantitative variation


Research in the Mackay lab focuses on understanding the genetic and environmental factors affecting variation in quantitative traits – traits for which phenotypic variation is continuously distributed in natural populations, with population variation often approximating a statistical normal distribution on an appropriate scale. The continuous variation arises from genetic complexity and environmental sensitivity. Quantitative genetic variation is the substrate for phenotypic evolution in natural populations and for selective breeding of domestic crop and animal species, and underlies susceptibility to common complex diseases and behavioral disorders in humans, as well as responses to pharmacological therapies. Our goal for understanding the genetic architecture of any quantitative trait is to peer within the black bell curve to elucidate the rules for translating genetic variation among individuals to phenotypic variation for the trait, at the level of primary variation in DNA sequence and intermediate phenotypes of transcript, protein and metabolite abundance, and in a range of relevant environments. We seek to answer the following questions:

•In what genes do mutations affecting the trait arise?

•In what subset of these genes do alleles affecting the trait segregate in natural populations?

•What is the distribution of allelic effects in nature?

•What are the pleiotropic effects on other traits, including reproductive fitness?

•Are interactions among these genes additive, or is there epistasis?

•Is allelic expression conditional on the physical or social environment?

•What is the molecular basis of allelic variation?

•Are causal variants in regulatory or coding regions; common or rare?

We use the Drosophila model system to address these questions, taking advantage of the genetic and genomic tools that can be used for the genetic dissection of quantitative traits:

•Screening P-element insertion mutations to identify candidate genes and pathways;

•Mapping quantitative trait loci (QTLs) by linkage to polymorphic molecular markers in crosses between genetically divergent strains, followed by complementation tests to deficiencies for high resolution mapping and to mutations to identify candidate genes;

•Mapping QTLs by associating molecular polymorphisms with quantitative phenotypes on a genome wide scale using our  Drosophila Genetic Reference Panel  of 192 inbred lines, for which complete genome sequence will be available in the near future;

•Incorporating variation in transcript abundance in these studies, to provide biological context to the QTLs and identify transcriptional and genetic networks affecting complex traits;

•Incorporating ecologically relevant environments in the above studies.

Our lab is currently focused on five broad topics:     evolutionary quantitative genetics the genetic architecture of complex behaviors ,   Drosophila models of human complex traits ,   speciation ,   and systems genetics of complex traits .