Monday, November 26, 2012

Scientists find that different cells contain different genomes

Basic, high-school level biology currently teaches that every cell in the human body contains the entire human genome, and that this genome is identical. The difference between a kidney cell and a brain cell has so far been believed to be in the expression of genes, and not the amino acid code itself.

Some scientists, though, have questioned the current dogma by positing that the copying of DNA from mother cells to daughter cells during human development is not 100% faithful, and that deletions, duplications and sequence changes occur.

Recently, a study conducted by Yale and Stanford scientists has helped give this hypothesis strong support. Using stem cells, the researchers have shown that "humans are made up of a mosaic of cells with different genomes", thereby debasing the longstanding belief that every cell contains the same genome.

The scientists used whole-genome sequencing to study stem cells (called iPS cells) that they developed from mature differentiated skin cells (i.e. matured daughter skin cells) of the inner upper arm area of two human families.

They compared these cells to the skin cells from which they originated (i.e. mother skin cells), and found that the iPS cell genomes closely resembled their mother cell genomes. However, there were deletions or duplications involving fairly large chunks of DNA (up to a thousand base pairs). Upon further inspection of where these differences first occurred, it was found that up to half these differences "pre-existed", i.e. already found among the mother skin cells and were not a result of deletions/duplications/changes during the copying of mother cell genome to daughter cells.

As it turns out, "mosaicism is extensive" in the cells of the skin. 30% of skin cells contain copy number variations (CNVs), meaning segments of DNA that are deleted or duplicated (without a change in sequence). These CNVs were previously only thought to occur in association with diseases such as cancer. These findings have huge implications because up till now, genetic analyses have only use blood samples. Evidently, blood cell genomes might be different from those of the cells of other parts of the body, and all work that has involved DNA (e.g. developing vaccines/medicine) may be missing mutations that exist outside of blood cells.

See the Yale article here
See another article here

Saturday, November 17, 2012

Ancestry Solves Disease Riddles

Being able to find the genetic roots of idiopathic diseases (diseases that arise spontaneously) is a crucial part of finding the cures and treatments for those illnesses. However, when human genomes have literally millions of genetic variations that could effectively cause a disease, looking for a particular mutation is like looking for a needle in a haystack; the task is near impossible. But what if there was a way that the amount of variations a researcher or doctor was choosing from was significantly decreased?

A new study by scientists at The Scripps Research Institute, Scripps Health, and Scripps Translational Institute has proven that looking at the genomes of people with similar ancestries dramatically reduces the amount of variations produced when comparing genomes, making finding a specific genetic mutation much easier. The scientists examined the genomes of 52 individuals from 10 different populations and ancestry and compared the amount of variations between the populations and between each individual genome. The results were as expected: within a specific population and ancestry, the amount of mutations were decreased and between individual genomes of different ancestry, the amount of mutations was drastically increased.

This find is important because it will encourage the sequencing of more human genomes for use in the medical world. The more genomes that are sequenced, the more genomes will be available to compare with when trying to find a genetic mutation that may be the cause of harmful diseases for which the cure was unknown. This will make finding the mutation easier diagnosing the disease quicker, and prescribing treatment or finding a cure more efficient and faster.


Thursday, November 15, 2012

Genetic Diversity in Cancer Cells

A recent study performed by Stefanie Jeffrey, MD (professor of surgery and chief of surgical oncology research at the Stanford University School of Medicine) and her research team has brought new insight into the heterogeneity of cancer cells and how we may be able to treat them. Through the use of two relatively new technologies (the Magsweeper and the PCR microfluidic chip) the researchers were able to isolate and sequence 95 genes from the circulating tumor cells of 50 patients with breast cancer. Circulating tumor cells, or CTCs, are a rare type of red blood cell believed to help disseminate cancer from organ to organ throughout the body. The results of the study reflected a surprising amount of genetic diversity in CTCs. “In the patients, we ended up with a subset of 31 genes that were most dominantly expressed,” said Jeffrey. “And by looking at levels of those genes, we could see at least two distinct groups of circulating tumors cells.” The researchers were able to divide the CTCs into as many as five groups, depending on which genes were used, each with different combinations of genes turned on and off. The diversity among these CTCs suggests that a single biopsy of a patient’s tumor does not necessarily indicate all of the molecular changes driving the cancer forward and helping it to spread. As we continue in our efforts to learn more about cancer and how to treat it, we must keep in mind that different cells may require different therapies.

According to an article published on the Stanford University School of Medicine website, this study is “the first time that scientists have used high-throughput gene analysis to study individual CTCs, and opens the door for future experiments that delve even more into the cell diversity. The Stanford team is now working on different methods of using CTCs for drug testing as well as studying the relationship between CTC genetic profiles and cancer treatment outcomes. They’ve also expanded their work to include primary lung and pancreatic cancers as well as breast tumors.”

1. “Not all tumor cells are equal: Stanford study reveals huge genetic diversity in cells shed by tumors” <>
2. “Not all tumor cells are equal: Study reveals genetic diversity in cells shed by tumors” <>
3. “Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines” <>

Wednesday, November 7, 2012

Inflammation Marker Linked to Increase Risk for Death From Cancer in Korean Men

Inflammation marker linked to increased risk for death from cancer in Korean men

PHILADELPHIA — Measuring blood levels of high-sensitive C-reactive protein, an important marker of inflammation, in apparently cancer-free men could potentially help identify those at increased risk for death from cancer, in particular lung cancer, according to data published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
"Inflammation has been linked to the initiation and progression of several types of cancer, as well as to the progression of atherosclerosis and cardiovascular disease," said Minseon Park, M.D., Ph.D., M.P.H., assistant professor in the Department of Family Medicine at the Center for Health Promotion at Seoul National University Hospital in South Korea. "We wanted to determine whether there was a relationship between a well-established marker of inflammation, high-sensitive C-reactive protein (hs-CRP), and death from all causes, death from cancer or death from a site-specific cancer in Koreans."
Park and colleagues retrospectively analyzed data from 33,556 individuals who had completed medical checkups, answered questions on cancer-related behavioral factors (like smoking status and exercise habits) and had been screened for blood hs-CRP at the health-screening center at Seoul National University Hospital between May 1995 and December 2006. During an average follow-up of 9.4 years, 1,054 deaths from all causes and 506 deaths from cancer were recorded.
When the researchers adjusted for several variables, including age, diabetes, smoking status and exercise habits, men with the highest level of hs-CRP in their blood (3 mg per liter or more) were 38 percent more likely to have died from any cause compared with men with the lowest hs-CRP level (1 mg per liter or less). They were also 61 percent more likely to have died from cancer.
For women, after adjusting for a number of variables, no statistically significant association was observed for hs-CRP level and death from any cause or death from cancer.
Through analysis of associations between hs-CRP levels and site-specific cancers, the researchers found that a significant relationship existed only for lung cancer. After adjusting for multiple variables, individuals with the highest hs-CRP level were more than twice as likely to die from lung cancer compared with those with the lowest hs-CRP level.
The association between hs-CRP levels and all-cause mortality and cancer mortality was stronger in lean individuals compared with those who were overweight.
"This was surprising," said Park. "Because obesity is a major risk factor for chronic diseases like cancer, physicians and the mass media often recommend eating less and exercising more. While an important public health message, some people are too concerned with these recommendations and they eat fewer calories than their body actually needs. It is important that we eat enough to meet the metabolic demands of our body to make sure our organs function adequately for a healthy life."

Arboreal and Bipdeal Ancestors

Australopithecus afarensis, a hominid and closely related human ancestor, was an upright-walking species, or bipedal. However, it has long been debated whether or not this species were also climbers who spent much of their time in trees. This has question has remained a mystery due to the fact that a complete set of A. afarensis shoulder blades had never been available to study. However, for the first time ever, David Green and Zeresenay Alemseged were able to analyze a complete set of shoulder blades and conduct a study on their ability to climb.

The two scientists took 11 years to extract the shoulder blades from a skeleton embedded in sandstone. The skeleton, named Selam, lived 3.3 million years ago. The extraction took so long because shoulder blades are extremely thin and rarely fossilize. When they do fossilize, they often fragment.

The scientists digitized the shoulder blades and compared them to fossils of other human relatives as well as other old world apes. They discovered that these shoulder blades were quite apelike, suggesting that this species was adapted to climbing in trees, in addition to its bipedalism.

This study is significant because it moves us closer to answering the question: When did our ancestors stop climbing? This study shows that this happened much later than previously thought. In addition, this study answers this question of arboreal adaptation that had been debated about for several decades.


Monday, November 5, 2012

A Theory of Human Longevity

Humans have an incredibly maximum potential life expectancy especially in comparison with our primate ancestors and our hunter-gatherer counterparts. The decline in mortality rate can be attributed to improvements in technology. Currently, a 65 year-old Japanese man is 200 times less likely to die than his hunter-gatherer counterpart. The Japanese man has an expected annual probability of death of 0.8%, compared to the 65 year-old hunter-gatherer with an expected annual probability of death of 5.3%.

Technology does not explain why humans posses a much higher maximum potential human lifespan. Today, because of our long life expectancy we are able to postpone aging and its detriments. We are able to pass down our genes before the effects of old age set in. This is the result of oocyte depletion, but oocyte depletion happens before the other defects of age occur. The short-finned pilot whale and the Asian elephant are the only other known species that experience the same post-reproductive phenomenon; In fact the average American woman lives 79.2 years, 30 of which are post reproductive.

A recent study modeled the Grandmother Hypothesis and found that even a small contribution of gradmothering was attributed to longer potential lifespan. In the study I found they assumed that only women above the age of 45 could be grandmother. At age two the study assumed that children are able to leave mothers for their grandmothers because they have gone through the nursing period, and at 3 the mother is able to have a second child. Then at 8.2 children reach the age of independence. So the grandmother cares for the child for 6.2 years. Under the assumptions of this study, eligible grandmothers initially make up less than 1% of females, but that proportion steadily increases to 43%. Showing the dramatic effect grandmothering has on increasing longevity

The reasoning for this is that grandmothers are able to supply food that the child cannot get himself; they also allow the mother to reproduce before her first child’s age of independence. Grandmothers are investing in their grandchildren’s lives to ensure the success of their genes. This gives credence to why menopause may have been selected.

This study does not disprove other theories as to why humans have a longer lifespan, but it is a narrow study that shows the benefits that the role of a grandmother has in evolution. 

Works Cited:
Brooks, Rob. "Is Human Longevity Due to Grandmothers or Older Fathers?" The Huffington Post., 31 Oct. 2012. Web. 05 Nov. 2012. <>.
Burger, Oksar, Annette Baudisch, and James W. Vaupel. "Human Mortality Improvement in Evolutionary Context." Proceedings of the National Academy of Science of the United States of America 109.44 (2012): n. pag. Print.
Kim, Peter S., James E. Coxworth, and Kristen Hawkes. "Increased Longevity Evolves from Grandmothering." Proceedings of the Royal Society Biological Sciences (2012): n. pag. Increased Longevity Evolves from Grandmothering. Web. 05 Nov. 2012. <>.
Kuhle, B. "An Evolutionary Perspective on the Origin and Ontogeny of Menopause." Maturitas 57.4 (2007): 329-37. Print.