UCLA researchers examine human embryonic stem cell genome

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UCLA researchers examine human embryonic stem cell genome

http://www.eurekalert.org/pub_releases/2008-03/uoc--ure032708.php

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 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.

In this study, Teitell and his team sought to determine copy number

variants (CNVs), or differences in the numbers of certain genes, in

two embryonic stem cell lines. The CNVs provide a unique genetic

fingerprint for each line, which can also indicate relatedness

between any two stem cell lines. Teitell used embryonic stem cell

lines that made different types of neurons and studied them with

array CGH for comparison. His team found CNV differences between the

two lines in at least seven different chromosome locations below the

level of detection using standard karyotype studies. Such differences

could impact the therapeutic utility of the lines and could have

implications in disease development. More studies will be required to

determine the effect of specific CNVs in controlling stem cell

function and disease susceptibility, he said.

" In studying embryonic stem cell lines in the future, if we find

differences in regions of the genome that we know are associated with

certain undesirable traits or diseases, we would choose against using

such stem cells, provided safer alternative lines are available, "

Teitell said.

Large genome-wide association studies are underway in a variety of

diseases to determine what genetic abnormalities might be at play.

When the genetic fingerprint or predisposing genes for a certain

disease is discovered, it could be used as key information in

screening embryonic stem cell lines.