Small differences in the human genome sequence underlie different degrees of susceptibility to disease and drug response between individuals. Sequencing of DNA is presently the best way to characterize these differences. Despite recent advances, current methods are still relatively expensive, time-consuming and do not provide information in a meaningful context. We are investigating approaches that have the potential to obtain DNA sequence directly in the context of its chromosomal position in the genome. Knowing chromosomal origin of a sequence is necessary to distinguish between the genetic contribution from each of the two parents. The precise location of a sequence on a chromosome is also necessary because a significant proportion of sequences are found more than once and at multiple locations within the genome and it is important to distinguish between these. Furthermore, it is becoming increasingly clear that variation in the number of copies and arrangement of particular sequences affect phenotype e.g. genetic disease. The Mir group is developing new methods to determine DNA base sequence as well as means to pinpoint the sequence reads to their actual location within an individual genome. This work will lead towards the goal of sequencing individual human genomes at ultra-low cost, which will be important for developing personalized forms of medicine.