Variation of CNV distribution in five different ethnic populations

White, Stefan J.; Vissers, Lisenka E.L.M.; Kessel, Ad Geurts van; Menezes, Renée X. de; Kalay, Ersan; Lehesjoki, Anna‐Elina; Giordano, Piero C.; Vosse, Esther van de; Breuning, Martijn H.; Brunner, Han G.; Dunnen, Johan T. den; Veltman, Joris A.

doi:10.1159/000106437

Cited by 47 publications

(46 citation statements)

References 73 publications

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“…Even when the inaccuracies of CNV boundary determination are considered, it appears likely that gain-and-loss CNVRs often reflect recurrent CNV changes, rather than heterozygosity in the reference genomes. We, and others, have demonstrated that CNV changes can be recurrent (White et al 2007;Turner et al 2008). …”

Section: Cnv Data Setsmentioning

confidence: 76%

“…Use of a reference pool also allows for an accurate estimation of the frequency of each CNV as well as the type of CNV (i.e., loss or gain). In a previous study (White et al 2007), we used multiplex ligation-dependent probe amplification (MLPA) (Schouten et al 2002;White et al 2004) and validated the presence and frequency of six recurrent CNVs. This showed an excellent correlation between these different approaches for CNVs identified using our BAC arrays.…”

Section: Methods Identification Of Nijmegen Cnvsmentioning

confidence: 99%

See 1 more Smart Citation

Reduced purifying selection prevails over positive selection in human copy number variant evolution

Nguyen¹,

Webber²,

Hehir-Kwa³

et al. 2008

Genome Res.

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Copy number variation is a dominant contributor to genomic variation and may frequently underlie an individual's variable susceptibilities to disease. Here we question our previous proposition that copy number variants (CNVs) are often retained in the human population because of their adaptive benefit. We show that genic biases of CNVs are best explained, not by positive selection, but by reduced efficiency of selection in eliminating deleterious changes from the human population. Of four CNV data sets examined, three exhibit significant increases in protein evolutionary rates. These increases appear to be attributable to the frequent coincidence of CNVs with segmental duplications (SDs) that recombine infrequently. Furthermore, human orthologs of mouse genes, which, when disrupted, result in pre-or postnatal lethality, are unusually depleted in CNVs. Together, these findings support a model of reduced purifying selection (Hill-Robertson interference) within copy number variable regions that are enriched in nonessential genes, allowing both the fixation of slightly deleterious substitutions and increased drift of CNV alleles. Additionally, all four CNV sets exhibited increased rates of interspecies chromosomal rearrangement and nucleotide substitution and an increased gene density. We observe that sequences with high G+C contents are most prone to copy number variation. In particular, frequently duplicated human SD sequence, or CNVs that are large and/or observed frequently, tend to be elevated in G+C content. In contrast, SD sequences that appear fixed in the human population lie more frequently within low G+C sequence. These findings provide an overarching view of how CNVs arise and segregate in the human population.

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Section: Cnv Data Setsmentioning

confidence: 76%

Section: Methods Identification Of Nijmegen Cnvsmentioning

confidence: 99%

Reduced purifying selection prevails over positive selection in human copy number variant evolution

Nguyen¹,

Webber²,

Hehir-Kwa³

et al. 2008

Genome Res.

View full text Add to dashboard Cite

show abstract

“…Much of this may be due to the fact that only recently has the extent of CNV between populations been studied. White et al (2007) examined CNV frequencies in twelve CNVRs, in five distinct populations and found differences in the distribution of CNVs between them. Jakobsson et al (2008) expanded their study to include 405 individuals from the Human Genome Diversity Project (Cann et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Statistical issues in the analysis of DNA Copy Number Variations

Kennedy

Erickson

Wojczynski

et al. 2008

IJCBDD

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Approaches to assess copy number variation have advanced rapidly and are being incorporated into genetic studies. While the technology exists for CNV genotyping, a further understanding and discussion of how to use the CNV data for association analyses is warranted. We present the options available for processing and analysing CNV data. We break these steps down into choice of genotyping platform, normalisation of the array data, calling algorithm, and statistical analysis.

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“…[8][9] Many such cohorts exhibited inter-and intra-population differences in CNV frequency distributions. [10][11][12][13][14][15][16][17][18][19][20][21][22] In addition to disease risk, these differences, furthermore, explain a significant proportion of normal phenotypic variation. [23][24][25][26] In this context, we characterized the genome-wide architecture of CNVs in 286 healthy, unrelated subjects characterized for musical aptitude and related traits.…”

Section: Introductionmentioning

confidence: 99%

The genome-wide landscape of copy number variations in the MUSGEN study provides evidence for a founder effect in the isolated Finnish population

et al. 2013

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Here we characterized the genome-wide architecture of copy number variations (CNVs) in 286 healthy, unrelated Finnish individuals belonging to the MUSGEN study, where molecular background underlying musical aptitude and related traits are studied. By using Illumina HumanOmniExpress-12v.1.0 beadchip, we identified 5493 CNVs that were spread across 467 different cytogenetic regions, spanning a total size of 287.83 Mb (B9.6% of the human genome). Merging the overlapping CNVs across samples resulted in 999 discrete copy number variable regions (CNVRs), of which B6.9% were putatively novel. The average number of CNVs per person was 20, whereas the average size of CNV per locus was 52.39 kb. Large CNVs (41 Mb) were present in 4% of the samples. The proportion of homozygous deletions in this data set (B12.4%) seemed to be higher when compared with three other populations. Interestingly, several CNVRs were significantly enriched in this sample set, whereas several others were totally depleted. For example, a CNVR at chr2p22.1 intersecting GALM was more common in this population (P ¼ 3.3706 Â 10 À44 ) than in African and other European populations. The enriched CNVRs, however, showed no significant association with music-related phenotypes. Moreover, the most common CNV locations in world's normal population cohorts (6q14.1, 11q11) were overrepresented in this population. Thus, the genome-wide CNV investigation in this Finnish sample set demonstrated features that are characteristic to isolated populations. Novel CNVRs and the functional implications of CNVs revealed in this study elucidate structural variation present in this population isolate, and may also serve as candidate gene loci for music-related traits.

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Variation of CNV distribution in five different ethnic populations

Cited by 47 publications

References 73 publications

Reduced purifying selection prevails over positive selection in human copy number variant evolution

Reduced purifying selection prevails over positive selection in human copy number variant evolution

Statistical issues in the analysis of DNA Copy Number Variations

The genome-wide landscape of copy number variations in the MUSGEN study provides evidence for a founder effect in the isolated Finnish population

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