Digital Genotyping of Macrosatellites and Multicopy Genes Reveals Novel Biological Functions Associated with Copy Number Variation of Large Tandem Repeats

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Here we utilize Nanostring digital assays and show their utility for estimating copy number of 186 multicopy genes and tandem repeats. By analyzing patterns of single nucleotide variation around these variants, we show that copy number variation at the vast majority of tandem repeat variations is not effectively tagged by nearby SNPs, and thus standard genome-wide association studies that focus on SNPs provide little or no information about such variants. By comparing patterns of tandem repeat copy number with variation in local gene expression and DNA methylation, we also identify extensive functional effects on local genome function. This includes an example of a non-coding macrosatellite repeat, expansion of which exerts a repressive effect on a nearby gene accompanied by accumulations of local DNA methylation. Finally, comparison of diverse human populations with a number of primate genomes shows that many of these sequences have undergone extreme changes in copy number during recent human and primate evolution, and show signatures that suggest possible selective effects. Overall, we conclude that multicopy genes and macrosatellites represent a highly variable fraction of the genome with important functional effects that has been systematically ignored by previous studies.

Vyšlo v časopise: Digital Genotyping of Macrosatellites and Multicopy Genes Reveals Novel Biological Functions Associated with Copy Number Variation of Large Tandem Repeats. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004418
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004418

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