The Value of Regenotyping Older Linkage Data Sets with Denser Marker Panels

Objectives: 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 selec...

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Bibliographic Details
Published in:Human heredity 2014-01, Vol.78 (1), p.9-16
Main Authors: Vieland, Veronica J., Walters, Kimberly A., Azaro, Marco, Brzustowicz, Linda M., Lehner, Thomas
Format: Article
Language:English
Subjects:
Chromosome Mapping - methods
Chromosome Mapping - statistics & numerical data
Databases, Genetic - statistics & numerical data
Family Health
Genetic Linkage
Genetic markers
Genome, Human - genetics
Genome-Wide Association Study - methods
Genome-Wide Association Study - statistics & numerical data
Genotype
Genotype & phenotype
Genotyping Techniques - methods
Genotyping Techniques - statistics & numerical data
Hispanic Americans - genetics
Hispanic Americans - statistics & numerical data
Humans
Linkage Disequilibrium
Microsatellite Repeats - genetics
Original Paper
Polymorphism
Polymorphism, Single Nucleotide
Reproducibility of Results
Satellite DNA
Schizophrenia - ethnology
Schizophrenia - genetics
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Summary:Objectives: 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.
ISSN:0001-5652
1423-0062
DOI:10.1159/000360003