SDSC resources, expertise used in genomic analysis of 115 year-old woman

April 30, 2014, University of California - San Diego

A team of researchers investigating the genome of a healthy supercentenarian since 2011 has found many somatic mutations – permanent changes in cells other than reproductive ones – that arose during the woman's lifetime. Led by Erik Sistermans and Henne Holstege from the VU University Medical Center in Amsterdam, the team recently published its findings in the journal Genome Research.

While previous studies have examined mutations that arise in certain disease conditions such as leukemia, Sistermans said that it was not well known how many mutations might appear in the genomes of , according to the GenomeWeb report.

At the time of her death at the age of 115, the subject woman, called W115 by the researchers, was the second oldest person in the world and showed no signs of vascular disease or dementia. By donating her body to science, she allowed researchers to study her organs and genome.

The researchers hypothesized that , which divide frequently, would have many more somatic mutations than , which seldom divide. Thus the whole genomes of W115's blood and brain cells were sequenced using SOLiD technology from Life Technologies. Analyses were then done to look for mutations present in the but not the brain cells.

These analyses involved numerous computations, some of which were done by Wayne Pfeiffer on the Triton cluster at the San Diego Supercomputer Center at the University of California, San Diego under a National Institutes of Health grant. Pfeiffer said that the initial analyses identified thousands of putative somatic mutations, many of which were incorrect because of sequencing errors. Filters were subsequently developed to select the mutations most likely to be somatic.

Two types of mutations were considered: single nucleotide variants (SNVs) and short insertions or deletions (indels). Filtering of the latter was particularly compute-intensive and was done at SDSC. Thousands of core hours were consumed, and some steps required more than 64 gigabytes of shared memory, according to Pfeiffer.

After filtering, many of the highly likely and moderately likely somatic mutations were tested by targeted sequencing using newer Ion PGM sequencers, also from Life Technologies.

Based on these validation tests, the researchers estimated that there were about 450 somatic mutations in the non-repetitive genome of the white blood cells studied, corresponding to an average of four mutations per year. These mutations, they noted, were not present in the breast cancer that W115 had at age 100 or in the gastric tumor she had at the time of her death. About 95% of the somatic mutations were SNVs rather than indels.

"Of 376 highly likely somatic SNVs, only four mapped to regions in genes that code for proteins, whereas most were in genomic regions predicted to have neither adverse nor favorable impact on genetic fitness," said Pfeiffer. "The message here is that one can have lots of somatic mutations and still live long, provided the mutations do not affect genetic fitness."

"It is important to note that white blood cells differ from most other cells in the body and are especially prone to acquiring somatic mutations," said Mark A. Miller from SDSC, who helped interpret the results. "Large numbers of white blood cells are generated from relatively few hematopoietic stem cells. Because white blood cells divide continually throughout a person's lifetime, it is possible for non-harmful to accumulate."

"These mutations accumulate in clones that comprise only some of the white blood cells, which makes their detection more difficult," explained Pfeiffer. "For W115, about 64% of the white blood cells comprised a dominant clone, which was where the mutations were found, while about 44% of the white blood cells were in a second clone subsidiary to the larger one. The remaining cells were presumably in smaller clones that were below our detection limit."

The researchers concluded that there is a significant somatic mutation background among white blood cells, even in healthy blood.

Explore further: Hundreds of genetic mutations found in healthy blood of a supercentenarian

Related Stories

Hundreds of genetic mutations found in healthy blood of a supercentenarian

April 23, 2014
Genetic mutations are commonly studied because of links to diseases such as cancer; however, little is known about mutations occurring in healthy individuals. In a study published online in Genome Research, researchers detected ...

Mutations in cancer often affect the X chromosome

October 18, 2013
Every case of cancer originates from changes in a person's genetic material (mutations). These usually occur as "somatic mutations" in individual cells during an individual's lifetime, rather than being inherited from a person's ...

ASH: CALR mutations ID'd in myeloproliferative neoplasms

December 10, 2013
(HealthDay)—Many patients with myeloproliferative neoplasms without mutations in the Janus kinase 2 gene (JAK2) or in the thrombopoietin receptor gene (MPL) have mutations in the CALR gene encoding calreticulin, according ...

Immunogenic mutations in tumor genomes correlate with increased patient survival

April 29, 2014
Developing immunotherapies for cancer is challenging because of significant variability among tumors and diversity in human immune types. In a study published online today in Genome Research, researchers examined the largest ...

Hundreds of random mutations in leukemia linked to aging, not cancer

July 19, 2012
Hundreds of mutations exist in leukemia cells at the time of diagnosis, but nearly all occur randomly as a part of normal aging and are not related to cancer, new research shows.

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

1 / 5 (1) May 01, 2014
Frank Holstege et al and Henne Holstege et al need to have a meeting of the minds. Frank's group examined nutrient-dependent pheromone-controlled changes in cell types that are clearly responsible for cell type differentiation in the cells of all individuals of all species, which are also associated with increased organismal complexity of their genomes and species diversification.

Henne's collaborators set out to determine the prevalence and types of mutations within the healthy blood of a human with genome of high complexity. Using calculations and the Single Nucleotide POLYMORPHISM database, they found Single Nucleotide VARIANTS that were not associated with disease. With the change in terms from 'normal' nutrient-dependent "polymorphisms" to "variants," the label of mutation seems to fit the healthy variants.

It is difficult for population geneticists to make terms like beneficial MUTATION "fit." But they fooled you, didn't they?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.