Optimal design of genetic studies of gene expression with two-color microarrays in outbred crosses.
Combining global gene-expression profiling and genetic analysis of natural allelic variation (genetical genomics) has great potential in dissecting the genetic pathways underlying complex phenotypes. Efficient use of microarrays is paramount in experimental design as the cost of conducting this type of study is high. For those organisms where recombinant inbred lines are available for mapping, the "distant pair design" maximizes the number of informative contrasts over all marker loci. Here, we describe an extension of this design, named the "optimal pair design," for use with F2 crosses between outbred lines. The performance of this design is investigated by simulation and compared to several other two-color microarray designs. We show that, for a given number of microarrays, the optimal pair design outperforms all other designs considered for detection of expression quantitative trait loci (eQTL) with additive effects by linkage analysis. We also discuss the suitability of this design for outbred crosses in organisms with large genomes and for detection of dominance.
Lam
Alex C
AC
Roslin Institute (Edinburgh), University of Edinburgh, Roslin Biocentre, Roslin, Midlothian, United Kingdom. alex.lam@roslin.ed.ac.uk
Fu
Jingyuan
J
Jansen
Ritsert C
RC
Haley
Chris S
CS
de Koning
Dirk-Jan
DJ
D000818:Animals; D002874:Chromosome Mapping; D003116:Color; D003198:Computer Simulation; D003433:Crosses, Genetic; D005456:Fluorescent Dyes; D015870:Gene Expression; D020869:Gene Expression Profiling; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D040641:Quantitative Trait Loci; D012107:Research Design
D005456:Fluorescent Dyes
Genetics. 2006 Oct;174(2):945-57
16888340
Science. 2002 Apr 26;296(5568):752-5
11923494
Behav Genet. 1972 Mar;2(1):3-19
4157472
Nat Genet. 2005 Nov;37(11):1224-33
16200066
Genetics. 2005 Sep;171(1):359-64
15956673
Nat Genet. 2001 Dec;29(4):389-95
11726925
Genetics. 1994 Mar;136(3):1195-207
8005424
PLoS Genet. 2006 Dec 29;2(12):e222
17196041
Trends Genet. 2001 Jul;17(7):388-91
11418218
PLoS Genet. 2005 Dec;1(6):e78
16362079
Bioinformatics. 2002 Feb;18(2):339-40
11847090
Genetics. 2004 Dec;168(4):2285-93
15611192
Nat Genet. 2005 Mar;37(3):225-32
15711547
Nature. 2004 Aug 12;430(7001):743-7
15269782
Nat Genet. 2005 Mar;37(3):243-53
15711544
Science. 1983 May 13;220(4598):671-80
17813860
Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1708-13
17237218
Nat Genet. 2007 Oct;39(10):1202-7
17873877
Physiol Genomics. 2006 Dec 13;28(1):15-23
16985008
Nature. 2003 Mar 20;422(6929):297-302
12646919
Nat Genet. 2005 Jul;37(7):710-7
15965475
Genetics. 2006 Mar;172(3):1993-9
16361243
Am J Hum Genet. 2004 Dec;75(6):1094-105
15514893
Trends Genet. 2005 Jul;21(7):377-81
15908034