I run a clinical molecular genetics diagnostic lab. Approximately 70% of the output is sequencing disease genes for pathological mutations. In recent weeks we have been hit by major problems where sequence quality is trashed by what appears to be n-1 products in the sequence traces. All primers (for all amplicons across many genes) are M13 tagged to allow universal sequencing of a large variety of templates. The n-1 problem goes across the board. We have had new M13 sequencing primers synthesised to the highest purity and experiments suggest the problem is template-related. I cannot understand why N-1 template should give N-1 sequencing product from a pure sequencing primer. Any suggestgions??