Genomics of subtelomeres: Technical problems, solutions and the future

Abstract

Genome projects invariably are missing the subtelomeric regions due to cloning, sequencing and informatic problems. The repetitive nature of these sequences and the shared homology between different subtelomeres in most organisms preclude assembly of the regions leaving them incomplete. This is clearly an issue when a great deal of interesting biology, as seen in the previous chapters, involves the subtelomeres. In some cases, organism-specific or individual strain-specific approaches have been used to obtain material for sequencing and analysis as well as assembly. However, a more general approach applicable to most organisms has been elusive. Various cloning techniques have been tried and developed with mixed success. The most promising general approach involves individual telomere regions cloned as yeast artificial chromosomes (YACs), isolating them from all the other subtelomeres that have overlapping homology. This is time-consuming, and there is still a bottleneck in sequencing these. New sequencing technologies may solve many of the technical problems, yet there are still informatic problems with assembly because of the repetitive nature of the regions. Although progress has been made, the solution to efficient completion of subtelomeric regions will likely take combined approaches, such as deep sequencing in pedigrees to look for genetic linkage (associations) with known segregating sites near the ends of chromosomes. An efficient and cost-effective approach is needed before individual genome projects can move into population genomics involving the subtelomeres which is crucial for studies of diversity in parasites as well as in quantitative genetic studies in many organisms.