Stem cell researchers from UCLA used a high resolution technique to examine the genome, or total DNA content, of a pair of human embryonic stem cell lines and found that while both lines could form neurons, the lines had differences in the numbers of certain genes that could control such things as individual traits and disease susceptibility.
The technique used to study the genome, which contains all the genes on 46 chromosomes, is called array CGH. The use of higher resolution techniques, such as array CGH and, soon, whole genome sequencing, will enhance the ability of researchers to examine stem cell lines to determine which are best – least likely to result in diseases and other problems – to use in creating therapies for use in humans.
Array CGH provided a much better look at the gene content on the chromosomes of human embryonic stem cells, with a resolution about 100 times better than standard clinical methods. Clinical specialists commonly generate a karyotype to examine the chromosomes of cancer cells or for amniocentesis in prenatal diagnosis, which has a much lower resolution than Array CGH, said Michael Teitell, a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and the senior author of the study. Small defects that could result in big problems later on could be missed using karyotyping for stem cells.
“Basically, this study shows that the genetic makeup of individual human embryonic stem cell lines is unique in the numbers of copies of certain genes that may control traits and things like disease susceptibility,” said Teitell, who also is an associate professor of pathology and laboratory medicine and a researcher at UCLA's Jonsson Comprehensive Cancer Center. “So, in choosing stem cell lines to use for therapeutic applications, you want to know about these differences so you don't pick a line likely to cause problems for a patient receiving these cells.”
The study appears in the March 27, 2008 express edition of the journal Stem Cells.
Differences between individual DNA sequences provide the basis for human genetic variability. Forms of variation include single DNA base pair alterations, duplications or deletions of genes or sets of genes, and translocations, a chromosomal rearrangement in which a segment of genetic material from one chromosome becomes heritably linked to another chromosome. These changes can be benign, but they can also promote diseases such as certain cancers, or confer increased risk to other diseases, such as HIV infection or certain types of kidney ailments.