Skin Cells Reveal DNA’s Genetic Mosaic
News Nov 19, 2012
Published in the Nov. 18 issue of Nature, the study paves the way for assessing the extent of gene variation, and for better understanding human development and disease.
“We found that humans are made up of a mosaic of cells with different genomes,” said lead author Dr. Flora Vaccarino, the Harris Professor of Child Psychiatry at the Yale Child Study Center. “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.”
The longstanding belief has been that our cells have the same DNA sequence and this blueprint governs the body’s functions. The Yale team’s research challenges this dogma. Some scientists have hypothesized that during development, when DNA is copied from mother to daughter cells, there could be deletions, duplications and changes in the sequence of the DNA, and an entire group of genes could be affected. This premise has been incredibly difficult to test, but Vaccarino and colleagues have done so in this new study.
The team used whole genome sequencing to study induced pluripotent stem cells lines (iPS), which are stem cells developed from a mature-differentiated cell. The team grew cells taken from the inner upper arms of two families. The team spent two years characterizing these iPS cell lines and comparing them to the original skin cells.
While observing that the genome of iPS cells closely resembles the genome of skin cells from which they originated, the team could identify several deletions or duplications involving thousands of base pairs of DNA. The team then performed additional experiments to understand the origin of those differences, and showed that at least half of them pre-existed in small fractions of skin cells. These differences were revealed in iPS cells because each iPS line is derived from one, or very few, skin cells. Vaccarino said these iPS lines could act as a magnifying glass to see the mosaic of genomic differences in the body’s cells.
“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,” said Vaccarino. “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.”
“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 added.
Vaccarino worked with a team of researchers from several laboratories, including those of Mark Gerstein, Sherman Weissman, Alexander Eckehart Urban, working together under the auspices of the Program in Neurodevelopment and Regeneration. Other authors on the study include 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.
Single-stranded Origami Technology Drives Drug Delivery Systems and Pharmaceutical Nanofactories ForwardNews
First nanotechnological approach enables the design and replication of complex single-stranded DNA and RNA origami with potential for drug delivery and nanofabrication.READ MORE
Cracking the Code of Coenzyme Q BiosynthesisNews
Coenzyme Q is a vital cog in the body’s energy-producing machinery, a kind of chemical gateway in the conversion of food into cellular fuel. Researchers are developing new tools to shed light on CoQ function, primarily by finding and defining proteins that have a direct link to the chemical. This includes the development of a new multi-omic strategy to identify the global function of an RNA-binding protein that has long been associated with mitochondria and its role in CoQ biosynthesis.READ MORE
First Successful Gene Therapy Trial Reported for People with Hemophilia ANews
Patients with hemophilia A who received a single infusion of an investigational gene therapy showed improved levels of the essential blood clotting protein FVIII, with 11 of 13 achieving normal or near-normal FVIII levels.READ MORE