Abstracts (first author)

Talk Plenary (Fri 23)

Charting the Genotype-Phenotype map: Lessons from Drosophila

Author(s): Mackay T

Summary:

Quantitative traits are affected by multiple interacting loci with individually small and environmentally sensitive effects. Knowledge of the detailed genetic architecture of quantitative traits is important from the perspectives of evolutionary biology, human health and plant and animal breeding. Understanding the genetic architecture of quantitative traits begins with identifying the genes regulating these traits, mapping the subset of genetically varying quantitative trait loci (QTLs) in natural populations, and pinpointing the molecular polymorphisms defining QTL alleles. Drosophila brings an impressive toolkit to the challenge of genetically dissecting quantitative traits. I will discuss insights into the complex genetic architecture of quantitative traits obtained from genome wide association mapping in the Drosophila melanogaster Genetic Reference Panel (DGRP), which consists of 192 sequenced inbred lines derived from the Raleigh, USA population. These studies indicate that epistatic gene action is common, and additivity can be an emergent property of underlying genetic interaction networks. Epistasis causes hidden quantitative genetic variation in natural populations, the potential for rapid speciation, and negatively impacts the predictive ability of additive models. These observations offer valuable lessons for understanding the genetic basis of variation for quantitative traits in other organisms.


Video


Abstracts (coauthor)

Summary:

Appropriate responses to chemical signals are essential for survival and reproduction, and genetic variation that gives rise to phenotypic variation in olfactory behaviour provides a substrate for natural selection. Drosophila melanogaster provides an ideal system to study the genetic basis for natural variation in olfactory behaviour because its olfactory system is well characterized and genetically identical individuals can be reared in controlled environments. The Drosophila melanogaster Genetic Reference Panel (DGRP), a collection of inbred wild-derived lines with fully sequenced genomes enables GWA studies to be performed in a scenario where all variants are known, candidate genes can be functionally tested allowing empirical assessment of the FDR, and outbred populations derived from DGRP lines can be constructed for the analysis of epistasis. GWA analysis together with variance GWA (vGWA) analysis in the DGRP revealed single nucleotide polymorphisms (SNPs) associated with variation in olfactory behaviour. Subsequent extreme QTL mapping using advanced intercross line (AIL) populations derived from lines with opposite extreme behavioural responses revealed additional SNPs. Combined analyses of GWA, vGWA and extreme QTL mapping uncovered a cellular network associated with variation in olfactory behaviour, centered on genes involved with cellular signaling and neural development. Candidate genes and network connectivity were validated through mutational analysis. We show that different elements of the genetic architecture underlying natural variation in olfactory behaviour are revealed in GWA studies and extreme QTL mapping contingent on allele frequencies and context-dependent effects, but they converge on similar cellular processes. Such genetic architecture appears to be a general feature of quantitative traits, is likely to be universal, and has profound implications for the interpretation of human GWA studies and the evolution of complex traits.

Contacts

Chairman: Octávio S. Paulo
Tel: 00 351 217500614 direct
Tel: 00 351 217500000 ext22359
Fax: 00 351 217500028
email: mail@eseb2013.com

Address

XIV Congress of the European Society for Evolutionary Biology

Organization Team
Department of Animal Biology (DBA)
Faculty of Sciences of the University of Lisbon
P-1749-016 Lisbon
Portugal

Website

Computational Biology & Population Genomics Group 
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