Mutant sperm guide clinicians to ne...( Research published today in Nature G...)

Research published today in Nature Genetics shows that some rearrangements of the human genome occur more frequently than previously thought. The work is likely to lead to new identification of genes involved in disease and to improve diagnosis of genomic disease.

The scientists from the Wellcome Trust Sanger Institute looked at four unstable regions in the genome where rearrangements cause genetic diseases, so-called 'genomic disorders', and found that some of these rearrangements were found in sperm much more frequently than expected.

In work published in November 2006, the team, led by Dr Matt Hurles, showed that losses or duplication of 'chunks' of the human genome occurred frequently in apparently healthy people. These losses or gains of DNA regions are called Copy Number Variants (CNVs), and can be found all over the genome in every individual.

Some of the mechanisms thought to produce CNVs would be expected to produce about one duplication for every deletion: however, clinical records for genomic disorders show only a few duplications, compared with hundreds of deletions.

"There was no direct, global measure of the relative rate at which human DNA is gained or lost, a study that requires many thousands of human genomes," explained Dr Matt Hurles, Investigator at the Wellcome Trust Sanger Institute, "so we carried out a study on four clinically important regions using human sperm cells as our population of genomes.

"Sperm cells give us an unbiased snapshot of CNVs: using our new highly-sensitive assays we can detect one rearrangement in a million cells."

The team looked at regions known to be affected by rearrangement in Williams-Beuren Syndrome, Charcot-Marie-Tooth disease Type 1A, Smith-Magenis Syndrome, and a deletion (AZFa) that causes male infertility. Their study showed that duplications are about half as frequent as deletions. By contrast, the two types of CNV are similarly common in healthy adu
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