title: The value of regenotyping older linkage data sets with denser marker panels.
abstract: OBJECTIVE
  Linkage analysis can help determine regions of interest in whole-genome sequence studies. However, many linkage studies rely on older microsatellite (MSAT) panels. We set out to determine whether results would change if we regenotyped families using a dense map of SNPs.
  
  
  METHODS
  We selected 47 Hispanic-American families from the NIMH Repository and Genomics Resource (NRGR) schizophrenia data repository. We regenotyped all individuals with DNA available from the NRGR on the Affymetrix Lat Array. After optimizing SNP selection for inclusion on the linkage map, we compared information content (IC) and linkage results using MSAT, SNP and MSAT+SNP maps.
  
  
  RESULTS
  As expected, SNP provided a higher average IC (0.78, SD 0.03) than MSAT (0.51, SD 0.10) in a direct 'apples-to-apples' comparison using only individuals genotyped on both platforms; while MSAT+SNP provided only a slightly higher IC (0.82, SD 0.03). However, when utilizing all available individuals, including those who had genotypes available on only one platform, the IC was substantially increased using MSAT+SNP (0.76, SD 0.05) compared to SNP (0.61, SD 0.02). Linkage results changed appreciably between MSAT and MSAT+SNP in terms of magnitude, rank ordering and localization of peaks.
  
  
  CONCLUSIONS
  Regenotyping older family data can substantially alter the conclusions of linkage analyses.
authors: Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
authors: Veronica J
authors: VJ
authors: Vieland
authors: Kimberly A
authors: KA
authors: Walters
authors: Marco
authors: M
authors: Azaro
authors: Linda M
authors: LM
authors: Brzustowicz
authors: Thomas
authors: T
authors: Lehner
mesh_terms: D002874:Chromosome Mapping / Q000379:methods* / Q000706:statistics & numerical data; D030541:Databases, Genetic / Q000706:statistics & numerical data; D005192:Family Health; D008040:Genetic Linkage; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods* / Q000706:statistics & numerical data; D006630:Hispanic or Latino / Q000235:genetics / Q000706:statistics & numerical data; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics