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Figure 4.4 Chromosomal distribution of copy number variation. Data from Whole Genome TilePath array platform for 269 dye-swap experiments. For a given chromosome, log2 ratios for each individual are shown superimposed. Gaps correspond to centromeric regions where data are not available. Reprinted by permission from Macmillan Publishers Ltd: Nature (Redon et al. 2006), copyright 2006.

Locke et al. 2006). There was, however, no difference in the observed frequency of deletions compared to duplications as might have been expected if this were the case, although deletions were three times shorter than duplications (43 kb versus 120 kb). In terms of genes which were involved in copy number variation, many were involved in cell adhesion and perception of smell and chemical stimuli. Nearly half of the regions known to be involved in genomic disorders such as DiGeorge syndrome (Box 5.2) and Williams-Beuren syndrome (Box 5.3) showed high levels of copy number polymorphism in this population of apparently healthy individuals (Redon et al. 2006).

Redon and colleagues also analysed copy number variation for evidence of population differentiation and clustering to suggest recent positive selection (Fig. 4.5) (Redon et al. 2006). A number of specific examples were found including CCL3LT, a chemokine multicopy gene previously shown to be associated with protection from human immunodeficiency virus type 1 (HIV-1) infection (Section 14.2.4) (Gonzalez et al. 2005). A further striking example the authors found was a duplication near to the

MAPT gene present only in the population of European ancestry: this region of chromosome 17 is implicated in neurodegenerative disease and is associated with a large inversion polymorphism subject to recent positive selection in Europeans (Section 5.5.2) (Stefansson et al. 2005).

4.2.3 Finding deletions across the genome within normal human populations

The extent of deletions in the human genome has only recently been investigated for phenotypically normal individuals. The availability of high density genotyping data for common SNPs across the genome from the International HapMap Project (Section 9.2.4) has allowed investigators to identify deletions (Conrad et al. 2006; McCarroll et al. 2006) and inversions (Bansal et al. 2007). Other investigators have used an oligonucleotide array comparative hybridization approach comparing data from individuals to the reference human genome to identify deletions (Hinds et al. 2006).

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European (CEU)

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