“This was the first paper to show association of copy number variation with a common disease in rodents and humans, and one of only two papers to show association between transmissible gene copy number variation and any human disease.”

Gene copy number variation is a new area of investigation. It has only been realized in the last three years that mammalian genomes have a very high rate of relatively stable, transmissible gene copy number variation, that affects 10’s to 100’s of kilobases of DNA, often affecting entire genes or blocks of genes. These polymorphisms are only just being tested for association with disease.

This was the first paper to show association of copy number variation with a common disease in rodents and humans, and one of only two papers to show association between transmissible gene copy number variation and any human disease.

Previously, it was believed that the sequence of each our genomes—the instruction book of life—differed by only a single letter, say in every thousand or so letters of the instruction book. In the last three years, it has been realized that whole sentences or even chapters of the instruction book are missing in each of us. In fact, the duplication or deletion of these blocks of the instruction book is probably part of the way in which we have evolved as humans to fight infectious disease or to improve our reproductive fitness.

This study has shown that such changes are not always beneficial. In fact, in this case, a reduced copy number, or even complete loss, of a single gene known as Fcgr3, places individuals at risk of developing a form of kidney failure in the disease lupus. This is a new type of disease mechanism that is probably a common cause of many diseases. More work is under way to establish how widespread this new mechanism of disease is in humans.

Because this was a new type of genome sequence variation, the tools are not readily available to complete this type of study. This required a painstaking use of old and new methods in order to establish the nature of these unexpected results.

It is likely that new diagnostic tests could be based on these results which would increase the case for the use of genomic technologies in managing patients with a wide range of common diseases.