title: Linkage analysis of the GAW14 simulated dataset with microsatellite and single-nucleotide polymorphism markers in large pedigrees.
abstract: Recent studies have suggested that a high-density single nucleotide polymorphism (SNP) marker set could provide equivalent or even superior information compared with currently used microsatellite (STR) marker sets for gene mapping by linkage. The focus of this study was to compare results obtained from linkage analyses involving extended pedigrees with STR and single-nucleotide polymorphism (SNP) marker sets. We also wanted to compare the performance of current linkage programs in the presence of high marker density and extended pedigree structures. One replicate of the Genetic Analysis Workshop 14 (GAW14) simulated extended pedigrees (n = 50) from New York City was analyzed to identify the major gene D2. Four marker sets with varying information content and density on chromosome 3 (STR [7.5 cM]; SNP [3 cM, 1 cM, 0.3 cM]) were analyzed to detect two traits, the original affection status, and a redefined trait more closely correlated with D2. Multipoint parametric and nonparametric linkage analyses (NPL) were performed using programs GENEHUNTER, MERLIN, SIMWALK2, and S.A.G.E. SIBPAL. Our results suggested that the densest SNP map (0.3 cM) had the greatest power to detect linkage for the original trait (genetic heterogeneity), with the highest LOD score/NPL score and mapping precision. However, no significant improvement in linkage signals was observed with the densest SNP map compared with STR or SNP-1 cM maps for the redefined affection status (genetic homogeneity), possibly due to the extremely high information contents for all maps. Finally, our results suggested that each linkage program had limitations in handling the large, complex pedigrees as well as a high-density SNP marker set.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, Maryland, USA. royang@mail.nih.gov
authors.forename: Xiaohong Rose
authors.initials: XR
authors.lastname: Yang
authors.forename: Kevin
authors.initials: K
authors.lastname: Jacobs
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Kerstann
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bergen
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Goldin
mesh_terms: D002874:Chromosome Mapping; D003198:Computer Simulation; D003226:Congresses as Topic; D030541:Databases, Genetic; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results
chemical_list: D005819:Genetic Markers