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Figure 4.8 Genetic variation between human and chimpanzee genomes. Reprinted by permission from Macmillan Publishers Ltd: Nature Genetics (Cooper et al. 2007), copyright 2007.

Figure 4.8 Genetic variation between human and chimpanzee genomes. Reprinted by permission from Macmillan Publishers Ltd: Nature Genetics (Cooper et al. 2007), copyright 2007.

genome-wide, large scale copy number variation were available from earlier study data generated by Redon and colleagues (Section 4.2.2) (Redon et al. 2006). The authors found significant association for copy number variation and gene expression for all classes of copy number variation - namely deletions, duplications, deletions/ duplications at a given locus, multiallelic, and complex (as classified by Redon and colleagues (2006)).

In a conservative analysis of 'high confidence' copy number variants, Stranger and coworkers reported association with 99 non-redundant genes across the four populations, of which 34% were significantly associated in at least two populations and 7% in all four populations (Stranger et al. 2007a). The authors estimated that 50% of effects were due to copy number variation modulating regulatory sequences within genes or in noncoding DNA, in some cases acting at a considerable distance from the gene. In the same study, the association of expression with SNP diversity was analysed (Section 11.4.1). For 700 000 SNPs, approximately four times as many expression phenotypes were found to be associated, although there was little overlap with those associated with copy number variants. Overall, Stranger and colleagues estimated that up to 17.7% of variation in heritable gene expression was explained by copy number variation. Given that the majority of copy number variants are small and thought to remain undetected using the detection technology employed, this figure is likely to be much greater.

4.4 Copy number variation, diet, and drug metabolism

4.4.1 Duplication of the salivary amylase gene and high starch diet

The gene encoding salivary amylase, AMY1, lies within a highly variable region of chromosome 1 p21.1 and is thought to have undergone tandem duplication events within the human lineage (Groot et al. 1989; lafrate et al. 2004). It was the most common large scale copy number variation identified in a genomic screen by lafrate and colleagues, present in half of individuals studied with relative gains and losses in equal numbers of people (lafrate et al. 2004).

Perry and coworkers found that among a cohort of European Americans, copy number variation for AMY1 significantly correlated with levels of salivary amylase protein (Perry et al. 2007). They hypothesized that copy number variation in AMY1 may vary between those populations with higher starch consumption (for example agricultural societies and specific hunter gatherer groups relying on starch-rich tubers such as the Hadza) compared to those with low starch diets (rainforest

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