Enhancing linkage analysis of complex disorders: an evaluation of high-density genotyping.
To explore the potential value of recently developed high-density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK multiple sclerosis linkage genome screen, using Applied Biosystems high-density microsatellite linkage mapping set, the Illumina BeadArray linkage mapping panel (version 3) and the Affymetrix GeneChip Human Mapping 10K array. We found that genotyping success, information extraction and genotyping accuracy were improved with all systems. These improvements were particularly marked with the SNP-based methods (Illumina and Affymetrix), with little difference between these. The extent of additional information extracted is considerable, indicating that reanalysis of existing multiplex families using these newer systems would substantially increase power.
Sawcer
Stephen J
SJ
University of Cambridge Neurology Unit, Addenbrooke's Hospital, UK. sjs1016@mole.bio.cam.ac.uk
Maranian
Mel
M
Singlehurst
Sara
S
Yeo
TaiWai
T
Compston
Alastair
A
Daly
Mark J
MJ
De Jager
Philip L
PL
Gabriel
Stacey
S
Hafler
David A
DA
Ivinson
Adrian J
AJ
Lander
Eric S
ES
Rioux
John D
JD
Walsh
Emily
E
Gregory
Simon G
SG
Schmidt
Silke
S
Pericak-Vance
Margaret A
MA
Barcellos
Lisa
L
Hauser
Stephen L
SL
Oksenberg
Jorge R
JR
Kenealy
Shannon J
SJ
Haines
Jonathan L
JL
D002874:Chromosome Mapping / Q000379:methods*; D005069:Evaluation Studies as Topic; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D006113:United Kingdom
D005819:Genetic Markers