title: High resolution discovery and confirmation of copy number variants in 90 Yoruba Nigerians.
abstract: BACKGROUND
  Copy number variants (CNVs) account for a large proportion of genetic variation in the genome. The initial discoveries of long (> 100 kb) CNVs in normal healthy individuals were made on BAC arrays and low resolution oligonucleotide arrays. Subsequent studies that used higher resolution microarrays and SNP genotyping arrays detected the presence of large numbers of CNVs that are < 100 kb, with median lengths of approximately 10 kb. More recently, whole genome sequencing of individuals has revealed an abundance of shorter CNVs with lengths < 1 kb.
  
  
  RESULTS
  We used custom high density oligonucleotide arrays in whole-genome scans at approximately 200-bp resolution, and followed up with a localized CNV typing array at resolutions as close as 10 bp, to confirm regions from the initial genome scans, and to detect the occurrence of sample-level events at shorter CNV regions identified in recent whole-genome sequencing studies. We surveyed 90 Yoruba Nigerians from the HapMap Project, and uncovered approximately 2,700 potentially novel CNVs not previously reported in the literature having a median length of approximately 3 kb. We generated sample-level event calls in the 90 Yoruba at nearly 9,000 regions, including approximately 2,500 regions having a median length of just approximately 200 bp that represent the union of CNVs independently discovered through whole-genome sequencing of two individuals of Western European descent. Event frequencies were noticeably higher at shorter regions < 1 kb compared to longer CNVs (> 1 kb).
  
  
  CONCLUSIONS
  As new shorter CNVs are discovered through whole-genome sequencing, high resolution microarrays offer a cost-effective means to detect the occurrence of events at these regions in large numbers of individuals in order to gain biological insights beyond the initial discovery.
authors.affiliation: Affymetrix, Inc, 3420 Central Expressway, Santa Clara, CA 95051, USA. hajime_matsuzaki@affymetrix.com
authors.forename: Hajime
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Rich
authors.initials: R
authors.lastname: Rava
authors.forename: Glenn K
authors.initials: GK
authors.lastname: Fu
mesh_terms: D022202:Chromosomes, Artificial, Bacterial; D005260:Female; D018628:Gene Dosage; D005828:Genetics, Population; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009549:Nigeria; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D009841:Oligonucleotides / Q000235:genetics; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D017422:Sequence Analysis, DNA
chemical_list: D009841:Oligonucleotides