Global analysis of uniparental disomy using high density genotyping arrays.
BACKGROUND
Uniparental disomy (UPD), the inheritance of both copies of a chromosome from a single parent, has been identified as the cause for congenital disorders such as Silver-Russell, Prader-Willi, and Angelman syndromes. Detection of UPD has largely been performed through labour intensive screening of DNA from patients and their parents, using microsatellite markers.


METHODS
We applied high density single nucleotide polymorphism (SNP) microarrays to diagnose whole chromosome and segmental UPD and to study the occurrence of continuous or interspersed heterodisomic and isodisomic regions in six patients with Silver-Russell syndrome patients who had maternal UPD for chromosome 7 (matUPD7).


RESULTS
We have devised a new high precision and high-throughput computational method to confirm UPD and to localise segments where transitions of UPD status occur. Our method reliably confirmed and mapped the matUPD7 regions in all patients in our study.


CONCLUSIONS
Our results suggest that high density SNP arrays can be reliably used for rapid and efficient diagnosis of both segmental and whole chromosome UPD across the entire genome.
Bruce
S
S
Department of Biosciences at Novum, Karolinska Institutet, Huddinge, Sweden.
Leinonen
R
R
Lindgren
C M
CM
Kivinen
K
K
Dahlman-Wright
K
K
Lipsanen-Nyman
M
M
Hannula-Jouppi
K
K
Kere
J
J
D002874:Chromosome Mapping / Q000379:methods*; D005260:Female; D016678:Genome; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods; D024182:Uniparental Disomy / Q000175:diagnosis* / Q000235:genetics*