Toward fully automated genotyping: Genotyping microsatellite markers by deconvolution
- Carnegie Mellon Univ., Pittsburgh, PA (United States)
Dense genetic linkage maps have been constructed for the human and mouse genomes, with average densities of 2.9 cM and 0.35 cM, respectively. These genetic maps are crucial for mapping both Mendelian and complex traits and are useful in clinical genetic diagnosis. Current maps are largely comprised of abundant, easily assayed, and highly polymorphic PCR-based microsatellite markers, primarily dinucleotide (CA){sub n} repeats. One key limitation of these length polymorphisms is the PCR stutter (or slippage) artifact that introduces additional stutter bands. With two (or more) closely spaced alleles, the stutter bands overlap, and it is difficult to accurately determine the correct alleles; this stutter phenomenon has all but precluded full automation, since a human must visually inspect the allele data. We describe here novel deconvolution methods for accurate genotyping that mathematically remove PCR stutter artifact from microsatellite markers. These methods overcome the manual interpretation bottleneck and thereby enable full automation of genetic map construction and use. New functionalities, including the pooling of DNAs and the pooling of markers, are described that may greatly reduce the associated experimentation requirements. 32 refs., 5 figs., 3 tabs.
- OSTI ID:
- 209914
- Journal Information:
- American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 5 Vol. 57; ISSN AJHGAG; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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INCLUDING NUCLEAR AND PARTICLE DETECTORS
55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 GENERAL AND MISCELLANEOUS
ACCURACY
AUTOMATION
BIOLOGICAL MARKERS
DIAGNOSIS
GENETIC MAPPING
GENOTYPE
HEREDITARY DISEASES
HUMAN CHROMOSOMES
HUMAN POPULATIONS
MICE
MUTATIONS
NUCLEOTIDES
POLYMERASE CHAIN REACTION
SIZE