Old Methods for New Ideas: Genetic Dissection of the Determinants of Gene Expression Levels

There is increasing interest in understanding the molecular basis of complex traits. Initially, the genetic dissection of quantitative traits involved measurements of gross phenotypes. Subsequently, specific physiological and developmental components of individual traits have been dissected. Most recently, the underlying mechanisms of inheritance have been studied through various approaches that are supported by modern technological and methodological advances, namely quantitative trait locus/loci (QTL) analysis (Mackay, 2001; Mauricio, 2001; Doerge, 2002) and mutant analysis (Rossant and Spence, 1998; Hughes et al., 2000) in genetics; genome sequencing (Jang et al., 1999; The Arabidopsis Genome Initiative, 2000; Mouse Genome Sequencing Consortium, 2002) and gene expression analysis (Duggan et al., 1999; Lipshutz et al., 1999) in genomics; and protein structure analysis (Service, 1999) and protein assay (Kodadek, 2001; MacBeath, 2002)

[1]  Z. Zeng Precision mapping of quantitative trait loci. , 1994, Genetics.

[2]  S. P. Fodor,et al.  High density synthetic oligonucleotide arrays , 1999, Nature Genetics.

[3]  M K Kerr,et al.  Bootstrapping cluster analysis: Assessing the reliability of conclusions from microarray experiments , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[4]  G. Churchill,et al.  Variation in gene expression within and among natural populations , 2002, Nature Genetics.

[5]  M. Bittner,et al.  Expression profiling using cDNA microarrays , 1999, Nature Genetics.

[6]  E. Lander,et al.  Detection of regulatory variation in mouse genes , 2002, Nature Genetics.

[7]  P. Brown,et al.  Parallel human genome analysis: microarray-based expression monitoring of 1000 genes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Karl W. Broman,et al.  A model selection approach for the identification of quantitative trait loci in experimental crosses , 2002 .

[9]  L. McIntyre,et al.  Combining mapping and arraying: An approach to candidate gene identification , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Daniel R. Richards,et al.  Dissecting the architecture of a quantitative trait locus in yeast , 2002, Nature.

[11]  Gary A. Churchill,et al.  Analysis of Variance for Gene Expression Microarray Data , 2000, J. Comput. Biol..

[12]  L. Kruglyak,et al.  Genetic Dissection of Transcriptional Regulation in Budding Yeast , 2002, Science.

[13]  J. Nap,et al.  Genetical genomics : the added value from segregation , 2001 .

[14]  G. Churchill,et al.  Statistical design and the analysis of gene expression microarray data. , 2001, Genetical research.

[15]  G. Churchill Fundamentals of experimental design for cDNA microarrays , 2002, Nature Genetics.

[16]  The Arabidopsis Genome Initiative Analysis of the genome sequence of the flowering plant Arabidopsis thaliana , 2000, Nature.

[17]  R. W. Doerge,et al.  Calculation of the minimum number of replicate spots required for detection of significant gene expression fold change in microarray experiments , 2002, Bioinform..

[18]  Neal S. Holter,et al.  Fundamental patterns underlying gene expression profiles: simplicity from complexity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[19]  G. Schuler,et al.  Making effective use of human genomic sequence data. , 1999, Trends in genetics : TIG.

[20]  N. Camp,et al.  Quantitative Trait Loci , 2002 .

[21]  Russell D. Wolfinger,et al.  The contributions of sex, genotype and age to transcriptional variance in Drosophila melanogaster , 2001, Nature Genetics.

[22]  Colin N. Dewey,et al.  Initial sequencing and comparative analysis of the mouse genome. , 2002 .

[23]  R. Doerge,et al.  Empirical threshold values for quantitative trait mapping. , 1994, Genetics.

[24]  Z B Zeng,et al.  Multiple trait analysis of genetic mapping for quantitative trait loci. , 1995, Genetics.

[25]  Lisa Chong,et al.  Whole-istic Biology , 2002, Science.

[26]  R. Mauricio Mapping quantitative trait loci in plants: uses and caveats for evolutionary biology , 2001, Nature Reviews Genetics.

[27]  Yudong D. He,et al.  Functional Discovery via a Compendium of Expression Profiles , 2000, Cell.

[28]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[29]  T. Kodadek Protein microarrays: prospects and problems. , 2001, Chemistry & biology.

[30]  Gavin MacBeath,et al.  Protein microarrays and proteomics , 2002, Nature Genetics.

[31]  R. Doerge Multifactorial genetics: Mapping and analysis of quantitative trait loci in experimental populations , 2002, Nature Reviews Genetics.

[32]  Detlef Weigel,et al.  Large-scale identification of single-feature polymorphisms in complex genomes. , 2003, Genome research.

[33]  K. Kinzler,et al.  Small changes in expression affect predisposition to tumorigenesis , 2002, Nature Genetics.

[34]  Christina Kendziorski,et al.  On Differential Variability of Expression Ratios: Improving Statistical Inference about Gene Expression Changes from Microarray Data , 2001, J. Comput. Biol..

[35]  J. Rossant,et al.  Chimeras and mosaics in mouse mutant analysis. , 1998, Trends in genetics : TIG.

[36]  Ritsert C. Jansen,et al.  Studying complex biological systems using multifactorial perturbation , 2003, Nature Reviews Genetics.

[37]  Z B Zeng,et al.  Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[38]  E. Lander,et al.  Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. , 1989, Genetics.

[39]  R. Stoughton,et al.  Genetics of gene expression surveyed in maize, mouse and man , 2003, Nature.

[40]  Trudy F. C. Mackay,et al.  Quantitative trait loci in Drosophila , 2001, Nature Reviews Genetics.

[41]  G. Churchill,et al.  Experimental design for gene expression microarrays. , 2001, Biostatistics.

[42]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[43]  S. R. Searle Linear Models , 1971 .