Category Archives: Transhuman News

Many people think of osteoarthritis as a kind of wear-and-tear disease, but theres clearly a genetic component at work here as well.

The researchers were studying a gene called GDF5 that Kingsleys laboratory first linked to skeletal growth in the early 1990s. GDF5 is involved in bone growth and joint formation, and mutations in the coding portion of the gene have been shown to cause malformations in leg-bone structure in mice. In humans, GDF5 mutations are associated with shorter stature and joint problems; in particular, two nucleotide changes immediately upstream of the gene have been strongly associated with a 1.2- to 1.8-fold increase in the risk of osteoarthritis.

In the new study, the researchers were interested in learning more about how the DNA sequences surrounding GDF5 might affect the genes expression. Often, these noncoding sequences contain key regulatory regions known as promoters and enhancers. Capellini, Chen and Cao were able to identify a previously unknown enhancer region they termed GROW1, which is several thousand nucleotides downstream of GDF5.

When the researchers analyzed the sequence of GROW1 in the 1,000 Genomes Project database, which collects and compares sequences from many human populations around the globe, they identified a single nucleotide change that is highly prevalent in Europeans and Asians but that rarely occurs in Africans. When they introduced this nucleotide change into laboratory mice, they found that it decreased the activity of GDF5 in the growth plates of the long bones of fetal mice.

Further research showed that this nucleotide change has been repeatedly favored during human evolution. Modern humans migrated from Africa between 50,000 and 100,000 years ago. But they werent the first to leave the continent. Neanderthals and Denisovans moved north into Europe and Asia about 600,000 years ago. Interestingly, the researchers found that the same GROW1 variant was found in the DNA of both ancient and modern humans in Europe and Asia.

However, theres a dark side to this stocky, hardy body type: The GDF5 variant that reduces bone length comes hand-in-hand with the two upstream nucleotide changes known to confer an increased risk for osteoarthritis.

Its clear that the genetic machinery around a gene can have a dramatic impact on how it works, said Capellini. The variant that decreases height is lowering the activity ofGDF5in the growth plates of the bone. Interestingly, the region that harbors this variant is closely linked to other mutations that affect GDF5 activity in the joints, increasing the risk of osteoarthritis in the knee and hip.

The potential medical impact of the finding is very interesting because so many people are affected, said Kingsley. This is an incredibly prevalent, and ancient, variant. Many people think of osteoarthritis as a kind of wear-and-tear disease, but theres clearly a genetic component at work here as well. Now weve shown that positive evolutionary selection has given rise to one of the most common height variants and arthritis risk factors known in human populations.

Researchers from the University of Waterloo in Ontario, Canada, also contributed to the study.

The research was supported by the National Sciences and Engineering Research Council of Canada, the Arthritis Foundation, the National Institutes of Health (grant AR42236), the Howard Hughes Medical Institute, the Milton Fund of Harvard, the China Scholarship Council and the Jason S. Bailey Fund of Harvard.

Stanfords Department of Developmental Biology also supported the work.

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Decreasing height, increasing arthritis risk evolutionarily advantageous for humans - Stanford Medical Center Report

Findings of a large, multi-institutional breast cancer study could lead to more personalized risk assessment for women of African heritage and hasten approaches to diagnosing aggressive breast cancers early and treat them effectively. While the odds of developing breast cancer are nearly the same in white and black women, black women are 42% more likely to die from the disease.

The study, published online May 4, 2017, in JAMA Oncology, was designed to understand the racial disparity in survival rates by beginning to unravel the germline genetic variations and tumor biological differences between black and white women with breast cancer.

People have long associated breast cancer mortality in black women with poverty, or stress, or lack of access to care, but our results show that much of the increased risk for black women can be attributed to tumor biological differences, which are probably genetically determined, says study author Olufunmilayo Olopade, MD, professor of medicine and human genetics at the University of Chicago.

The good news, she says, is that as we learn more about these genetic variations, we can combine that information with clinical data to stratify risk and better predict recurrences especially for highly treatable cancers and develop interventions to improve treatment outcomes.

This is a great example of how team science and investments in science can accelerate progress in identifying the best therapies for the most aggressive breast cancers, says co-author Charles Perou, PhD, a member of the University of North Carolina Lineberger Comprehensive Cancer Center and professor of genetics, and pathology & laboratory medicine at the UNC School of Medicine.

In the largest dataset to date that has good representation of tumors from black women, we did not find much difference between the somatic mutations driving tumors in black and white women, he says. Yet, black women were more likely to develop aggressive molecular subtypes of breast cancer. Now we provide data showing that differences in germline genetics may be responsible for up to 40% of the likelihood of developing one tumor subtype versus another.

The study used DNA data collected from 930 women154 of predominantly African ancestry and 776 of European ancestryavailable through The Cancer Genome Atlas (TCGA), established by the National Cancer Institute and the National Human Genome Research Institute. Researchers combed through the data methodically, looking for racial differences in germline variations (normal DNA), somatic mutations (tumor acquired), subtypes of breast cancers, survival time, as well as gene expression, protein expression and DNA methylation patterns.

The crucial long-term benefit of this study, according to Olopade, is that it is a step toward the development of polygenic biomarkers, tools that can help us better understand each patients prognosis and, as we learn more, play a role in choosing the best treatment.

Genes matter, she says. This is a foot in the door for precision medicine, for scientifically targeted treatment.

Managed care executives need to learn how to do population risk stratification so they can get better outcomes for ALL patientsblack and white, Olopade adds. It is no longer acceptable to see the widening disparities in survival among black and white and not develop interventions to reduce it.

Breast cancer is not one disease, and it impacts women differentially, she says. We now have very effective treatment for the most aggressive breast cancers, and we should make sure all patients benefit from genomic testing. We also need to make sure that women get the right treatment at the right time based on their level of risk. We can no longer practice as if one size fits all.

Managed care should cover genetic testing and comprehensive risk assessment at diagnosis and promote accurate diagnosis to get the best therapies for (their) enrollees. (They) should promote access to clinical trials. It pays high dividend to get it right and not have to treat advanced cancers.

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Racial genes disparity in breast cancer mortality linked to genes - ModernMedicine

BBC News

Chief medical officer calls for gene testing revolution BBC News "I want the NHS across the whole breadth to be offering genomic medicine - that means diagnosis of our genes - to patients where they can possibly benefit," her report says. People with rare diseases could benefit from having greater access to the ... Gene testing could revolutionise cancer treatmentITV News All cancer patients should have their DNA tested to save lives, Chief Medical Officer saysTelegraph.co.uk Call for revolutionary DNA cancer care on NHSSky News The Sun -The Times (subscription) all 29 news articles »

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Chief medical officer calls for gene testing revolution - BBC News

A single gene mutation that helped early humans survive in Europe and Asia during the Ice Age may alsoincrease the risk of arthritis in modern-day humans.

Researchers from the Stanford University School of Medicine and Harvard University have found a gene mutation thathelped our ancestors survive colder temperatures by coding for shorter limbs, according to new research published in the journal Nature Genetics.

As modern humans migrated out of Africa between 50,000 and 100,000 years ago during the last Ice age, they were faced with colder temperatures.Agenetic variant for shorter limbs may have helped thembetterwithstandfrostbite, the researchers argue. Shorter bones also meant there was less chance of breaking a bone if they slipped on ice.

Theres a downside, however.The gene in question, known as GDF5, which isinvolved in bone growth and joint formation,also increases one'srisk of osteoarthritisa condition that causes joints to become painful and stiff. In humans, mutations in the GDF5 gene have been shown to belinked to a 1.2 to 1.8 times increase in the risk of osteoarthritis.

Of course, the prospect of painful joints is not a pretty one, nor particularly useful if youre hunting mammoths inIce AgeEurope. However, the risk from cold temperatures may have outweighed the risk ofosteoarthritis,which usually occurs after prime reproductive years. The gene was repeatedly favored as early humans migrated out of Africa and moved into colder corners of the world. Its thought that at least half of Europeans and Asians have the gene variant, yet it remains relatively rare in African populations.

Because its been positively selected, this gene variant is present in billions of people, David Kingsley, professor of developmental biology at Stanford, said in astatement. So even though it only increases each persons risk by less than twofold, its likely responsible for millions of cases of arthritis around the globe."

Armed with thisfresh insight, Professor Kingsley believes their study could havepractical implications in the world of medicine.

"This is an incredibly prevalent, and ancient, variant. Many people think of osteoarthritis as a kind of wear-and-tear disease, but theres clearly a genetic component at work here as well," he added. "Now weve shown that positive evolutionary selection has given rise to one of the most common height variants and arthritis risk factors known in human populations.

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Gene That Helped Humans Survive Migration Out Of Africa Increases Arthritis Risk - IFLScience