Having More Than One Set of DNA Carries Legacy of Risk

Mosaics don't only occur from mutations. They can be a result of two embryos that start out as fraternal twins, where some cells of the other twin get combined with the other, or even a total merging of the two twins into one embryo. Of course, the same thing could happen with identical twins, but would not create a mosaic because the celss are genetically the same.

http://www.nytimes.com/2014/07/31/science/having-more-than-one-set-of-dna-carries-legacy-of-risk.html?_r=1

JULY 31, 2014
Carl Zimmer

When Meriel M. McEntagart, a geneticist at St. George’s University of London, met the family in May 2012, she suspected that three of the children had a rare genetic disorder called Smith-Magenis syndrome. They had many of the symptoms of the disease, such as trouble sleeping through the night. Dr. McEntagart confirmed that diagnosis with a genetic test. The children were all missing an identical chunk of a gene known as RAI1.

One of the children had a different father from the other two, and so the mother could be the only source of their altered gene. But when Dr. McEntagart ran a standard blood test on the mother, the results were not nearly so straightforward: The woman had a normal version of RAI1.

Dr. McEntagart and her colleagues suspected that the answer to this puzzle was that the mother was a genetic mosaic.

We tend to think of ourselves as having just one set of genetic material, which exists in identical form in every one of our cells. But sometimes, people have two or more significantly different genomes. As our cells divide, some may go through a major mutation. So some individuals end up with groups of cells that have very different DNA from the rest of them.

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Dr. McEntagart got wind that researchers at Baylor College of Medicine in Houston were developing new methods for pinpointing mosaics, and they confirmed that the mother was indeed a mosaic. Some of her cells carried the Smith-Magenis syndrome mutation.

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In a study released Thursday in the American Journal of Human Genetics, the Baylor team and its colleagues describe the biggest search for cases in which mosaic parents passed down disease-causing mutations to their children. It turns out to be far from a fluke.

“This happens a surprising amount of the time,” said Chad A. Shaw, a co-author of the new study.

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The majority of the mother’s blood cells had intact copies of the RAI1 gene, the scientists found. But 25 percent of the cells lacked the same piece that was missing from the children’s genes.

The scientists argue that there’s only way to explain these strange results: The mother became a mosaic when she was a tiny clump of embryonic cells.

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the line of cells with the defective RAI1 gene gave rise to some of the mother’s eggs, some of her blood and perhaps some of her other tissues as well.

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