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3 December 2007
Mutant Sperm Could Be Cause Of Genetic Diseases
by George Atkinson

Scientists from the Wellcome Trust Sanger Institute have found that genetic diseases, caused by rearrangements of the human genome, occur more frequently than previously thought and are found in sperm much more frequently than expected.

Writing in Nature Genetics, 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 Hurles, "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."

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 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 adults, suggesting that some deletions are too detrimental for the genome to tolerate.

"It is likely that deletions are more harmful than duplications, perhaps because a vital gene is removed, and so less likely to survive," explained Hurles. "However, for some of the genomic regions we looked at, duplications can cause milder symptoms."

"Although some of these CNVs arise much more frequently than anyone thought, they are still comfortingly rare: we see them in about 1 in 50,000 sperm cells," explained Hurles. "These are unfortunate accidents of the essential shuffling of our genetic deck of cards, a process essential to human life. We need a new deal for each new person."

Related articles:
Mr. Sperm Goes To War
Aged Sperm Causing Pregnancies To Fail
Older Sperm Behind Genetic Mutations
Older Fathers Risk Children With Schizophrenia
Abnormal Sperm Result From Vasectomy Reversal

Source: Wellcome Trust Sanger Institute




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