For many common human diseases most of the genetic basis of inherited susceptibility remains to be elucidated. Some may be encoded by common susceptibility alleles, which can be detected by association studies based on linkage disequilibrium maps. However, a significant proportion may be attributable to multiple rare variants, each of which accounts for a very small proportion of the familial risk of disease. In the relatively near future it will become possible to sequence the complete human genome, or biologically interesting components such as all protein coding exons, in large numbers of disease cases and controls to identify all variants, common and rare, disease-causing and innocuous. This systematic screen of the coding sequences of the X chromosome in XLMR illustrates some of the strengths of large-scale resequencing in disease gene identification, but also highlights its pitfalls and challenges.
