title: Influence of marker heterozygosity and genetic heterogeneity on fine mapping.
abstract: The purpose of the current study was to utilize the Genetic Analysis Workshop 12 simulated data to evaluate fine-mapping strategies for quantitative traits. We approached the analysis as if it was a follow-up to a genome scan that had identified two regions of interest and used the provided 1-cM density microsatellite typing data to mimic fine mapping of these regions. As these investigators knew the true locations of the putative genes under study, we explored the effects of the informativeness of microsatellite markers (marker heterozygosity) and the effects of genetic heterogeneity across families for ten replicates of the data. These results shed a cautionary light on the reliability of fine-mapping efforts on refining mapping locations as the position and the strength of the lod score can be markedly affected by the sampling of the population, the amount of variation accounted for by the gene, and the informativeness of the marker. Our studies did not reveal a large effect of unlinked families on the shape of the lod score peak.
authors.affiliation: Neurology Department, Boston University School of Medicine, 715 Albany Street, Boston, MA 02145, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Heard-Costa
authors.forename: S
authors.initials: S
authors.lastname: Demissie
authors.forename: A L
authors.initials: AL
authors.lastname: DeStefano
authors.forename: B A
authors.initials: BA
authors.lastname: Knowlton
authors.forename: N E
authors.initials: NE
authors.lastname: Maher
authors.forename: R H
authors.initials: RH
authors.lastname: Myers
authors.forename: J S
authors.initials: JS
authors.lastname: Volcjak
authors.forename: J B
authors.initials: JB
authors.lastname: Wilk
authors.forename: L A
authors.initials: LA
authors.lastname: Cupples
mesh_terms: D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D019655:Quantitative Trait, Heritable
chemical_list: D005819:Genetic Markers