Genomewide linkage searches for Mendelian disease loci can be efficiently conducted using high-density SNP genotyping arrays.
Genomewide linkage searches aimed at identifying disease susceptibility loci are generally conducted using 300-400 microsatellite markers. Genotyping bi-allelic single nucleotide polymorphisms (SNPs) provides an alternative strategy. The availability of dense SNP maps coupled with recent technological developments in highly paralleled SNP genotyping makes it practical to now consider the use of these markers for whole-genome genetic linkage analyses. Here, we report the findings from three successful genomewide linkage analyses of families segregating autosomal recessively inherited neonatal diabetes, craniosynostosis and dominantly inherited renal dysplasia using the Affymetrix 10K SNP array. A single locus was identified for each disease state, two of which are novel. The performance of the SNP array, both in terms of efficiency and precision, indicates that such platforms will become the dominant technology for performing genomewide linkage searches.
Sellick
Gabrielle S
GS
Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, UK.
Longman
Cheryl
C
Tolmie
John
J
Newbury-Ecob
Ruth
R
Geenhalgh
Lynn
L
Hughes
Simon
S
Whiteford
Margo
M
Garrett
Christine
C
Houlston
Richard S
RS
D000595:Amino Acid Sequence; D003398:Craniosynostoses / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment