@article{norga_gurganus_dilda_yamamoto_lyman_patel_rubin_hoskins_mackay_bellen_2003, title={Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development}, volume={13}, ISSN={["0960-9822"]}, DOI={10.1016/S0960-9822(03)00546-3}, abstractNote={Background: The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5′ of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation.Results: Here, we have tested the efficacy of this strategy by assessing the extent to which screening for quantitative effects of P elements on sensory bristle number can identify genes affecting neural development. We find that such quantitative screens uncover an unusually large number of genes that are known to function in neural development, as well as genes with yet uncharacterized effects on neural development, and novel loci.Conclusions: Our findings establish the use of quantitative trait analysis for functional genome annotation through forward genetics. Similar analyses of quantitative effects of P element insertions will facilitate our understanding of the genes affecting many other complex traits in Drosophila.}, number={16}, journal={CURRENT BIOLOGY}, author={Norga, KK and Gurganus, MC and Dilda, CL and Yamamoto, A and Lyman, RF and Patel, PH and Rubin, GM and Hoskins, RA and Mackay, TF and Bellen, HJ}, year={2003}, month={Aug}, pages={1388–1397} }
 @article{anholt_dilda_chang_fanara_kulkarni_ganguly_rollmann_kamdar_mackay_2003, title={The genetic architecture of odor-guided behavior in Drosophila: epistasis and the transcriptome}, volume={35}, ISSN={["1546-1718"]}, DOI={10.1038/ng1240}, abstractNote={We combined transcriptional profiling and quantitative genetic analysis to elucidate the genetic architecture of olfactory behavior in Drosophila melanogaster. We applied whole-genome expression analysis to five coisogenic smell-impaired (smi) mutant lines and their control. We used analysis of variance to partition variation in transcript abundance between males and females and between smi genotypes and to determine the genotype-by-sex interaction. A total of 666 genes showed sexual dimorphism in transcript abundance, and 530 genes were coregulated in response to one or more smi mutations, showing considerable epistasis at the level of the transcriptome in response to single mutations. Quantitative complementation tests of mutations at these coregulated genes with the smi mutations showed that in most cases (67%) epistatic interactions for olfactory behavior mirrored epistasis at the level of transcription, thus identifying new candidate genes regulating olfactory behavior.}, number={2}, journal={NATURE GENETICS}, author={Anholt, RRH and Dilda, CL and Chang, S and Fanara, JJ and Kulkarni, NH and Ganguly, I and Rollmann, SM and Kamdar, KP and Mackay, TFC}, year={2003}, month={Oct}, pages={180–184} }
 @article{dilda_mackay_2002, title={The genetic architecture of drosophila sensory bristle number}, volume={162}, number={4}, journal={Genetics}, author={Dilda, C. L. and Mackay, T. F. C.}, year={2002}, month={Dec}, pages={1655–1674} }
 @article{wayne_hackett_dilda_nuzhdin_pasyukova_mackay_2001, title={Quantitative trait locus mapping of fitness-related traits in Drosophila melanogaster}, volume={77}, ISSN={["0016-6723"]}, DOI={10.1017/S0016672300004894}, abstractNote={We examined the genetic architecture of four fitness-related traits (reproductive success, ovariole 
number, body size and early fecundity) in a panel of 98 Oregon-R × 2b3 recombinant inbred lines 
(RILs). Highly significant genetic variation was observed in this population for female, but not 
male, reproductive success. The cross-sex genetic correlation for reproductive success was 0·20, 
which is not significantly different from zero. There was significant genetic variation segregating in 
this cross for ovariole number, but not for body size or early fecundity. The RILs were genotyped 
for cytological insertion sites of roo transposable elements, yielding 76 informative markers with an 
average spacing of 3·2 cM. Quantitative trait loci (QTL) affecting female reproductive success and 
ovariole number were mapped using a composite interval mapping procedure. QTL for female 
reproductive success were located at the tip of the X chromosome between markers at cytological 
locations 1B and 3E; and on the left arm of chromosome 2 in the 30D–38A cytological region. 
Ovariole number QTL mapped to cytological intervals 62D–69D and 98A–98E, both on the third 
chromosome. The regions harbouring QTL for female reproductive success and ovariole number 
were also identified as QTL for longevity in previous studies with these lines.}, number={1}, journal={GENETICAL RESEARCH}, author={Wayne, ML and Hackett, JB and Dilda, CL and Nuzhdin, SV and Pasyukova, EG and MacKay, TFC}, year={2001}, month={Feb}, pages={107–116} }
 @article{nuzhdin_dilda_mackay_1999, title={The genetic architecture of selection response: Inferences from fine-scale mapping of bristle number quantitative trait loci in Drosophila melanogaster}, volume={153}, number={3}, journal={Genetics}, author={Nuzhdin, S. V. and Dilda, C. L. and Mackay, T. F. C.}, year={1999}, month={Nov}, pages={1317–1331} }
 @article{nuzhdin_pasyukova_dilda_zeng_mackay_1997, title={Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster}, volume={94}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.94.18.9734}, abstractNote={
            Senescence, the decline in survivorship and fertility with increasing age, is a near-universal property of organisms. Senescence and limited lifespan are thought to arise because weak natural selection late in life allows the accumulation of mutations with deleterious late-age effects that are either neutral (the mutation accumulation hypothesis) or beneficial (the antagonistic pleiotropy hypothesis) early in life. Analyses of
            Drosophila
            spontaneous mutations, patterns of segregating variation and covariation, and lines selected for late-age fertility have implicated both classes of mutation in the evolution of aging, but neither their relative contributions nor the properties of individual loci that cause aging in nature are known. To begin to dissect the multiple genetic causes of quantitative variation in lifespan, we have conducted a genome-wide screen for quantitative trait loci (QTLs) affecting lifespan that segregate among a panel of recombinant inbred lines using a dense molecular marker map. Five autosomal QTLs were mapped by composite interval mapping and by sequential multiple marker analysis. The QTLs had large sex-specific effects on lifespan and age-specific effects on survivorship and mortality and mapped to the same regions as candidate genes with fertility, cellular aging, stress resistance and male-specific effects. Late age-of-onset QTL effects are consistent with the mutation accumulation hypothesis for the evolution of senescence, and sex-specific QTL effects suggest a novel mechanism for maintaining genetic variation for lifespan.
          }, number={18}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Nuzhdin, SV and Pasyukova, EG and Dilda, CL and Zeng, ZB and Mackay, TFC}, year={1997}, month={Sep}, pages={9734–9739} }