This opened up the possibility of having a unique marker for the defective allele in every family segregating haemophilia A. At first, with the expensive and laborious sequencing methods available, it was

necessary to screen using techniques that could show altered behaviour in a small fragment, which was then sequenced [17]. The advent of first generation sequencing machines made it feasible to sequence an entire coding region without a screening step. It meant that we could find a mutation in one-to-two weeks. As a result of this sequencing, Epigenetics inhibitor it soon became evident that there was no plausible disease-causing mutation in about half the severely affected cases. Jane Gitschier returned to the F8 gene to show that, in such cases, there was an inversion involving either

of two copies of an intronic gene F8A located within intron 22 and an extragenic copy of F8A located 400 kb upstream [18]. The international haemophilia A database, which I started in 1991 [19] to improve understanding of the correlation this website between mutation and phenotype, went online in 1996 [20]. From a critical analysis of the mutations published up to that date, we discovered that some mutations had a highly variable phenotype and that there was a stronger risk of inhibitor development for some types of mutation than others [21]. The database has grown steadily and as of 2004 listed over 1000 unique mutations. This is set to increase massively with the next update and overhaul of the site in 2012. The most recent technical advance in detection of foetal DNA in maternal blood now allows the status of a foetus to be determined as early as week 11 of gestation [22]. In the next 50 years, genetic tools will come to dominate not only diagnosis but treatment of the haemophilias, which after all are the classic

example of genetic disorder in man. Many recent enhancements to processes Cytidine deaminase used in genetic analysis of inherited bleeding disorders are available. They are reviewed here following the pathway from patient referral to reporting of results. Computer-based laboratory information management systems (LIMS) can provide a complete system of ‘paperless’ sample management. All patient referral documentation can be scanned and stored electronically, work lists can be generated for testing to be undertaken, and results can subsequently be recorded within the LIMS. Genomic DNA can be prepared from blood and other tissues using a variety of automated extraction procedures. Bar-coding of individual samples and of the plates in which they are analysed facilitates recording storage location and ensures that the correct samples are transferred between containers during analysis. Several genetic analysis techniques are available, generally utilizing genomic DNA as template.