Quadruplex MAPH: improvement of throughput in high-resolution copy number screening.
BACKGROUND
Copy number variation (CNV) in the human genome is recognised as a widespread and important source of human genetic variation. Now the challenge is to screen for these CNVs at high resolution in a reliable, accurate and cost-effective way.


RESULTS
Multiplex Amplifiable Probe Hybridisation (MAPH) is a sensitive, high-resolution technology appropriate for screening for CNVs in a defined region, for a targeted population. We have developed MAPH to a highly multiplexed format ("QuadMAPH") that allows the user a four-fold increase in the number of loci tested simultaneously. We have used this method to analyse a genomic region of 210 kb, including the MSH2 gene and 120 kb of flanking DNA. We show that the QuadMAPH probes report copy number with equivalent accuracy to simplex MAPH, reliably demonstrating diploid copy number in control samples and accurately detecting deletions in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) samples.


CONCLUSIONS
QuadMAPH is an accurate, high-resolution method that allows targeted screening of large numbers of subjects without the expense of genome-wide approaches. Whilst we have applied this technique to a region of the human genome, it is equally applicable to the genomes of other organisms.
Tyson
Jess
J
Institute of Genetics, School of Biology, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK. jess.tyson@nottingham.ac.uk
Majerus
Tamsin Mo
TM
Walker
Susan
S
Armour
John Al
JA
D022202:Chromosomes, Artificial, Bacterial; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D015342:DNA Probes; D018628:Gene Dosage; D015723:Gene Library; D015894:Genome, Human; D006801:Humans; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000379:methods*; D017422:Sequence Analysis, DNA
D015342:DNA Probes; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein