Profiling of copy number variations (CNVs) in healthy individuals from three ethnic groups using a human genome 32 K BAC-clone-based array.
To further explore the extent of structural large-scale variation in the human genome, we assessed copy number variations (CNVs) in a series of 71 healthy subjects from three ethnic groups. CNVs were analyzed using comparative genomic hybridization (CGH) to a BAC array covering the human genome, using DNA extracted from peripheral blood, thus avoiding any culture-induced rearrangements. By applying a newly developed computational algorithm based on Hidden Markov modeling, we identified 1,078 autosomal CNVs, including at least two neighboring/overlapping BACs, which represent 315 distinct regions. The average size of the sequence polymorphisms was approximately 350 kb and involved in total approximately 117 Mb or approximately 3.5% of the genome. Gains were about four times more common than deletions, and segmental duplications (SDs) were overrepresented, especially in larger deletion variants. This strengthens the notion that SDs often define hotspots of chromosomal rearrangements. Over 60% of the identified autosomal rearrangements match previously reported CNVs, recognized with various platforms. However, results from chromosome X do not agree well with the previously annotated CNVs. Furthermore, data from single BACs deviating in copy number suggest that our above estimate of total variation is conservative. This report contributes to the establishment of the common baseline for CNV, which is an important resource in human genetics.
Díaz de Ståhl
Teresita
T
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Sandgren
Johanna
J
Piotrowski
Arkadiusz
A
Nord
Helena
H
Andersson
Robin
R
Menzel
Uwe
U
Bogdan
Adam
A
Thuresson
Ann-Charlotte
AC
Poplawski
Andrzej
A
von Tell
Desiree
D
Hansson
Caisa M
CM
Elshafie
Amir I
AI
Elghazali
Gehad
G
Imreh
Stephan
S
Nordenskjöld
Magnus
M
Upadhyaya
Meena
M
Komorowski
Jan
J
Bruder
Carl E G
CE
Dumanski
Jan P
JP
D000465:Algorithms; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D015321:Gene Rearrangement; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008297:Male; D008390:Markov Chains; D020411:Oligonucleotide Array Sequence Analysis; D044469:Racial Groups / Q000235:genetics*; D044465:White People / Q000235:genetics