Mon, 19 Nov 2012 11:45 UTC
Researchers at the Yale School of Medicine set out to challenge the theory that human cells are comprised of identical genetic material, and that a body's functions are governed by that blueprint. They set out to test a competing hypothesis - that as DNA is copied from mother to daughter cells, deletions, duplications, and alternations to the sequence of the DNA could occur, and could affect entire groups of genes.
According to the university, that notion has been "incredibly difficult to test," but Dr. Flora Vaccarino, a professor of child psychology at Yale, and colleagues did so by using whole genome sequencing to analyze induced pluripotent stem cells (iPS) taken from the upper, inner arms of a pair of different families.
They spent 24 months characterizing those iPS cell lines and comparing them to the skin cells from which they originated, and while the genomes of each cell group were similar, Dr. Vaccarino's team was able to pinpoint multiple deletions or duplications that involved thousands of base pairs of DNA, the university explained.
Additional research showed that at least half of the variations they observed pre-existed in a small percentage of skin cells. Those differences were noticeable in the iPS cells because each line of those stem cells originated from either a single or an extremely limited number of skin cells.
"We found that humans are made up of a mosaic of cells with different genomes," Dr Vaccarino said in a statement. "We saw that 30 percent of skin cells harbor copy number variations (CNV), which are segments of DNA that are deleted or duplicated. Previously it was assumed that these variations only occurred in cases of disease, such as cancer. The mosaic that we've seen in the skin could also be found in the blood, in the brain, and in other parts of the human body."
"In the skin, this mosaicism is extensive and at least 30 percent of skin cells harbor different deletion or duplication of DNA, each found in a small percentage of cells," she added. "The observation of somatic mosaicism has far-reaching consequences for genetic analyses, which currently use only blood samples. When we look at the blood DNA, it's not exactly reflecting the DNA of other tissues such as the brain. There could be mutations that we're missing."
Vaccarino's team, which also included fellow researchers Mark Gerstein, Sherman Weissman, Alexander Eckehart Urban, Alexej Abyzov, Jessica Mariani, Dean Palejev, Ying Zhang, Michael Seamus Haney, Livia Tomasini, Anthony Ferrandino, Lior A. Rosenberg Belmaker, Anna Szekely, Michael Wilson, Arif Kocabas, Nathaniel E. Calixto, Elena L. Grigorenko, Anita Huttner, and Katarzyna Chawarska, published their findings in Sunday's edition of the journal Nature.
"These findings are shaping our future studies, and we're doing more studies of the developing brains of animals and humans to see if this variation exists there as well," Vaccarino said.