Methods for Precise Sizing, Automated Binning of Alleles and Reduction
of Error Rates in Large-Scale Genotyping Using Fluorescently-Labeled
Dinucleotide Markers.  Soumitra Ghosh, Zarir Karanjawala, Elizabeth
Hauser, Delphine Ally, Julie Knapp, Joseph Rayman, Anjene Musick,
Joyce Tannenbaum, Catherine Te, Shane Shapiro, William Eldridge,
Tiffany Musick, Colin Martin, Jeffrey Smith, John Carpten, Michael
Brownstein, John Powell, Raymond Whiten, Peter Chines, Stella Nylund,
Victoria Magnuson, Michael Boehnke, Francis Collins, and the FUSION
Study Group.  Genome Research, February 1997.

Large-scale genotyping is required to generate dense identity-by descent
maps to map genes for human complex disease.  In some studies the number
of genotypes needed can approach or even exceed a million.  Generally,
linkage and linkage disequilibrium analyses depend on clear allele
identification and subsequent allele frequency estimation.  Accurate
grouping or categorization of each allele in the sample (allele calling
or "binning") is therefore an absolute requirement.  Hence a genotyping
system that can reliably achieve this is necessary.  In the case of
affected sib-pair analysis without parents, the need for accurate allele
calling is even more critical.  We describe methods that permit precise
sizing of alleles across multiple gels using the fluorescence-based ,
Applied Biosystems (ABI) genotyping technology and discuss ways to
reduce genotyping error rates.  Using database utilities we show how to
minimize inter-gel allele size variation, to combine data effectively
from different models of ABI sequencing machines, and automatically bin
alleles.  The final data can then be converted into a format ready for
analysis by statistical genetic packages such as MENDEL.