Association mapping of disease loci, by use of a pooled DNA genomic screen.
Genomic screening to map disease loci by association requires automation, pooling of DNA samples, and 3,000-6,000 highly polymorphic, evenly spaced microsatellite markers. Case-control samples can be used in an initial screen, followed by family-based data to confirm marker associations. Association mapping is relevant to genetic studies of complex diseases in which linkage analysis may be less effective and to cases in which multigenerational data are difficult to obtain, including rare or late-onset conditions and infectious diseases. The method can also be used effectively to follow up and confirm regions identified in linkage studies or to investigate candidate disease loci. Study designs can incorporate disease heterogeneity and interaction effects by appropriate subdivision of samples before screening. Here we report use of pooled DNA amplifications-the accurate determination of marker-disease associations for both case-control and nuclear family-based data-including application of correction methods for stutter artifact and preferential amplification. These issues, combined with a discussion of both statistical power and experimental design to define the necessary requirements for detecting of disease loci while virtually eliminating false positives, suggest the feasibility and efficiency of association mapping using pooled DNA screening.
Barcellos
L F
LF
Department of Integrative Biology, University of California, Berkeley 94720, USA.
Klitz
W
W
Field
L L
LL
Tobias
R
R
Bowcock
A M
AM
Wilson
R
R
Nelson
M P
MP
Nagatomi
J
J
Thomson
G
G
D016022:Case-Control Studies; D002648:Child; D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D004247:DNA / Q000097:blood*; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D006432:Hemochromatosis / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats
D004247:DNA