Scientists map cell's DNA history to embryonic origin

Date: Jun-30-2014The fertilization of an egg gives rise to a genetically unique cell lineage that

unfolds as cell division ensues - eventually to produce a mature organism that in the case of

humans comprises some 100 million, million cells. Meanwhile, over the lifetime of the organism,

cellular DNA accumulates mutations that are not inherited from parental DNA - these so-called

"somatic" mutations carry a record of the lifetime experiences of each cell.

Now scientists in the UK have found a way to reconstruct the genetic life history of individual

cells back to their origins in the fertilized egg. They report their findings in the journal

Nature.

The achievement could help us better understand diseases like cancer, as senior author Mike

Stratton, professor and director of the Wellcome Trust Sanger Institute in Cambridge explains:

"...by looking at the numbers and types of mutation in each cell we will be able to obtain a

diary, writ in DNA, of what each healthy cell has experienced during its lifetime, and then

explore how this changes in the range of human diseases."

The team sequenced DNA of cells from different types of tissue

In their paper, Prof. Stratton and colleagues explain how they developed the approach by

looking at cells from the stomach, large and small bowel, and prostate of mice.

They cultured the single cells to produce enough DNA to carry out sufficiently accurate genome

sequencing.

When they compared cell DNA from one type of tissue to that of another, they found differences

in the numbers of mutations the different cells had accumulated - which they suggest is probably because of the

differences in rates of cell division.

Each time a cell divides, its DNA accumulates small changes. Think of transcribing a page of

writing - there is a small chance that a couple of typos or accidental changes creep in. Now think

of millions of pages, and transcribing them all again and again.

Patterns - as well as rates - of mutation varied among the cell types

But the team found it was not only the numbers of mutations that were different among the

different cell types, but also the patterns. They say this suggests the cells have been exposed to

different types of DNA damage and repair, reflecting their different lifetime experiences.

As not only the numbers of mutations were different among the different cell types, but also the patterns, the team suggests the cells have been exposed to different types of DNA damage and repair.

Back to the document analogy - the body attempts to put right any copying errors that creep in

with DNA repair processes - rather like proofreaders checking over typescripts.

So, by looking at the numbers and types of mutations in a cell's DNA, the team could work out

if it had divided only a few or many times - and also detect the imprints or "signatures" of DNA

damage that the cell had undergone over the life of the organism.

The other thing they did was compare mutation pattern and rates among the different cell types, which helped them map a detailed tree of development from the fertilized egg.

The authors point out that they were working with healthy mice, but if the mutation rates are

similar in humans, then it may well be possible to use their methods to study the life histories

of human cells.

First author Dr. Sam Behjati, also of the Sanger Institute, says:

"If we can better understand how normal, healthy cells mutate as they divide over a person's

lifetime, we will gain a fundamental insight into what can be considered normal and how this

differs from what we see in cancer cells."

Meanwhile, Medical News Today recently reported how researchers are paving the way

for virus-like DNA nanodevices to

diagnose disease and make drugs. One of the barriers to using "smart DNA nanorobots" to

diagnose diseases like cancer or target drugs directly to chosen tumors, or even manufacture them

on the spot, has been how to get them to evade the immune system. In this new study, a team from

Harvard's Wyss Institute for Biologically Inspired Engineering in Boston, MA, shows how.

Written by Catharine Paddock PhD

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.