Exon-centric regulation of ATM expression is population-dependent and amenable to antisense modification by pseudoexon targeting.

ATM is an important cancer susceptibility gene that encodes a critical apical kinase of the DNA damage response (DDR) pathway. We show that a key nonsense-mediated RNA decay switch exon (NSE) in ATM is repressed by U2AF, PUF60 and hnRNPA1. The NSE activation was haplotype-specific and was most promoted by cytosine at rs609621 in the NSE 3' splice-site (3'ss), which is predominant in high cancer risk populations.

Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations.

Background: An understanding of linkage disequilibrium (LD) structures in the human genome underpins much of medical genetics and provides a basis for disease gene mapping and investigating biological mechanisms such as recombination and selection. Whole genome sequencing (WGS) provides the opportunity to determine LD structures at maximal resolution.

Results: We compare LD maps constructed from WGS data with LD maps produced from the array-based HapMap dataset, for representative European and African populations.