Researchers identify the extraordinary genetic diversity -
In the most comprehensive genetic study of the Mexican population to date, UC San Francisco researchers and Stanford University and the National Institute of genomic Medicine of Mexico (INMEGEN), identified the considerable genetic diversity, reflecting thousands of years of separation between local people and the light on a number of aspects of confusion of Latino health.
The study, which documented nearly 1 million genetic variants from more than 1,000 people, revealed genetic differences as large as the variation between some Europeans and Asians, indicating populations that have been isolated for hundreds of thousands of years.
These differences provide an explanation for the wide variety of health factors among Latinos of Mexican origin, including different rates of breast cancer and asthma, as well as the therapeutic response. The results of the study on which UCSF and Stanford shared the first two and senior authors, appear in the June 13, 2014 online edition of the journal Science .
"Over thousands of years, there was a huge language and cultural diversity throughout Mexico, with large empires such as the Aztecs and Mayans, and small isolated populations" said Christopher Gignoux, PhD, who was the first author of the study with Andres Moreno Estrada, first as a graduate student at UCSF and now as a postdoctoral fellow at Stanford. "Not only have we been able to measure this diversity across the country, but we have identified the considerable genetic diversity, with implications for the actual disease based on where, exactly, your ancestors are from Mexico."
For decades, doctors on the basis of a range of diagnoses on patients, "said or perceived ethnic heritage, including the basic measures for lung capacity, which are used to determine whether a patient's lungs are damaged by disease or environmental factors. In this context, categories such as Latino or African American, two people reflect various combinations of genetic ancestry can be dangerously misleading and cause both misdiagnoses and incorrect treatment.
Although there have been many diseases / genetic studies from the human genome project, they mainly focused on the European and Euro-American populations, the researchers said. Accordingly, there is very little knowledge of the genetic basis of health differences between the various populations.
"In lung diseases such as asthma or emphysema, we know that what matters ancestry you to specific locations on your genes," said Esteban González Burchard, MD, MPH Professor of bioengineering and therapeutic Sciences and medicine in the UCSF school of pharmacy and medicine. Burchard is co-senior author of the paper with Carlos Bustamante, PhD, professor of genetics at Stanford. "In this study, we realized that for the classification of the disease, it is also important what kind of Amerindian descent you. Regarding genetics, it is the difference between a neighborhood and a specific address. "
The researchers focused on Mexico as one of the most important sources of pre-Columbian diversity, with long history of complex civilizations that have different contributions to the current population. Working collaboratively across institutions, the team enlisted 40 experts, from bi-lingual anthropologists statistical geneticists, biologists and clinicians calculation and researchers from several institutions in Mexico and others in England, France, Puerto Rico and Spain.
the study covered most geographic regions in Mexico and 511 people representing 20 indigenous 11 and mestizo population (ethnically mixed). Their information was compared with genetic data and measure lung from two previous studies, including about 250 Mexican and American children of Mexican origin in the genetics of asthma Latin Americans (GALA) study, the largest genetic study of Latino children in the United States, which led Burchard.
Among the results was the discovery of three distinct genetic groups in different regions of Mexico, and the clear remains of ancient empires through seemingly remote geographical areas. In particular, the Seri people along the northern mainland coast of the Gulf of California and a Mayan people known as the Lacandon, near the Guatemalan border, are genetically different from each other that Europeans are Chinese.
"We were surprised that this composition is also reflected in people with mixed ancestries cosmopolitan areas," said co-first author Andres Moreno Estrada, MD, PhD, Associate science research life at Stanford. "Hidden among the blocks of European and African descent, indigenous genetic map looks like a map of Mexico."
The study also revealed a dramatic difference in lung capacity among Métis people of western native Mexican descent and those of Eastern ancestry, to the extent that in a lung test of two people also healthy the same age, someone from the west might seem like a decade younger than the counterpart of the Yucatan. Burchard said this was clinically significant and could have important implications in the diagnosis of lung diseases.
Significantly, the study found that these genetic origins directly correlated with lung function in modern Mexican-Americans. Consequently, the research lays the foundation for further research and develop an accurate diagnosis and possibly the treatment on the basis of these genetic variations. It also creates a potentially important tool for public health policy, particularly in Mexico, the allocation of resources for research and care.
"This can shape public health and public policy," said Burchard. "If you test a group of children who are at risk of asthma or other health conditions, you want do in an area where the frequency of the disease gene is highest. We now have a map of Mexico that will help researchers make these clinical decisions and public health. "
Burchard, a pulmonologist whose work focuses on the impact of genetic ancestry on the risk of asthma and response to drugs against asthma in children, wanted to study the Mexican population since 03, both as a medical context for Mexican-American and as an opportunity to understand the Native American genetics. to do this, he reached out to Bustamante, who directs the Stanford Center for Computational, Evolutionary and human genomics.
"We were particularly motivated by the fact that the vast majority of genetic studies have focused on lowering European populations," said Bustamante. "We believe there are many possibilities for understanding biology and understanding the differences in the results of the disease in different parts of the world, studying the genetics of complex diseases in different populations. "
over the past few years, researchers have began to understand that genetic variation has a very particular structure, Bustamante said. Some common genetic variants reach appreciable frequency (eg, 30-50 percent) in many populations worldwide. Most of them seem to have existed in the human gene pool at the time of the great human diasporas, including migration out of Africa. However, Bustamante said a "huge wave" of other mutations have arisen since then that human populations have increased due to the advent and adoption of agriculture. These are much more rare, occurring in about 1 to 2 percent of the population, and are considered the two most recent and relevant to health and disease. These rare variants make up most of the genetic changes that we see in human populations.
Many of these genetic differences are already known to have a direct impact on our risk for certain diseases, such as the BRCA gene in breast cancer, or our ability to metabolize drugs. But before we can develop more precise or to prescribe the right patient therapies, we need much more knowledge of what these variants are among populations, and how they affect health.
"This is driving the ball down the field toward precision medicine," Burchard said. "We can not clump together and call on European Americans or Mexican Americans. There was much resistance to the study of racially mixed populations, because they were considered too complex. We believe offers real scientific advantage. "
complete results and a complete list of authors can be found in the paper, which appears online in Sciencemag.org. A representative picture of a diverse genome reflecting the varied heritage in the genes of an individual, can be found on the website of Burchard Lab.
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