An international group of researchers today unveiled a detailed map of human genetic variation within the major histocompatibility complex (MHC), the most important region of the human genome encoding the human response to infection, autoimmune disease and organ transplantation.
The work represents a milestone in the analysis of genetic variability for this fundamental immune region and lays the scientific foundation for future efforts aimed at uncovering the genetic roots of immune-related diseases. The findings of this international team, which includes scientists from the Montreal Heart Institute (MHI), the Université de Montréal (UdeM), the Broad Institute of MIT and Harvard and several other research institutions, appear in the September 24 advance online edition of Nature Genetics.
"This new map will be a key resource for researchers to use to find genes affecting health, disease, and responses to medications," said senior author Dr. John D. Rioux, PhD, who is associate professor of medicine at the UdeM and at the MHI where he works as a researcher and director of the Laboratory in Genetics and Genomic Medicine of Inflammation (www.inflammgen.org), visiting scientist of the Broad Institute of MIT and Harvard, and holder of the Canada Research Chair in Genetics and Genomic Medicine of Inflammation. "It will provide the information necessary to design powerful studies to identify the genetic risk factors located within the MHC."
The MHC -- specifically, the genes that comprise it -- is associated with more diseases than any other region of the human genome. This includes common diseases such as atherosclerosis, arthritis, diabetes, HIV, lupus, multiple sclerosis and Crohn's disease. However, pinpointing the specific changes that are causative in these diseases has been complicated by two factors: the extremely high degree of genetic diversity that exists in the MHC among different individuals and the tendency for multiple genetic differences in this region to be inherited together in groups called "haplotypes."
To characterize the haplotype patterns of the MHC, the researchers analyzed the variability in its DNA sequence in more than 350 individuals from diverse geographic regions, including Africa, Europe, China and Japan. Specifically, the researchers "read" ~7,500 single-letter changes in the genetic code called single nucleotide polymorphisms (SNPs) together with short segments of DNA sequence from a set of highly variable genes within the MHC, called "HLA genes." These genes form a distinctive fingerprint that is recognized by an individual's immune system to distinguish foreign tissues from "self" tissues and the genes' DNA sequences are frequently analyzed (a process called "HLA typing") in patients who receive organ transplants or suffer from autoimmune disease.
Importantly, the researchers' data and analyses, which are made available online to the entire scientific community, provide the tools needed to begin the initial efforts toward identifying genetic risk factors in the MHC for common immune-mediated diseases. Such endeavors, involving researchers at the Montreal Heart Institute, the University of California, San Francisco and the Broad Institute of MIT and Harvard, are now underway for several immune system diseases.
In addition, the results offer insights into the evolutionary history of the MHC region -- its early origins and the evolutionary forces that have helped to shape it over time. The findings also suggest that analyzing select SNPs within the HLA genes may offer a more economical alternative for characterizing the most common genetic variants in the region than standard HLA typing methods.
Nearly three-quarters of the DNA samples that the scientists analyzed had been previously examined as part of the International Haplotype Map ("HapMap") Project, a worldwide scientific collaboration to catalogue human genetic variation on a genome-wide scale. The latest findings, particularly the analyses of the HLA gene region, provide new and complementary information that can be integrated with data from the recently completed HapMap Project as well as other genomic efforts, to provide a comprehensive view of genetic variability in the human MHC.
Drug discovery: First rational strategy to find molecular glue degraders
03.08.2020 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften
Chlamydia: Greedy for Glutamine
03.08.2020 | Julius-Maximilians-Universität Würzburg
“Core-shell” clusters pave the way for new efficient nanomaterials that make catalysts, magnetic and laser sensors or measuring devices for detecting electromagnetic radiation more efficient.
Whether in innovative high-tech materials, more powerful computer chips, pharmaceuticals or in the field of renewable energies, nanoparticles – smallest...
An international research team with Prof. Cornelia Denz from the Institute of Applied Physics at the University of Münster develop for the first time light fields using caustics that do not change during propagation. With the new method, the physicists cleverly exploit light structures that can be seen in rainbows or when light is transmitted through drinking glasses.
Modern applications as high resolution microsopy or micro- or nanoscale material processing require customized laser beams that do not change during...
Although no life has been detected on the Martian surface, a new study from astrophysicist and research scientist at the Center for Space Science at NYU Abu...
New approach creates synthetic layered magnets with unprecedented level of control over their magnetic properties
The magnetic properties of a chromium halide can be tuned by manipulating the non-magnetic atoms in the material, a team, led by Boston College researchers,...
Scientists of Tomsk Polytechnic University jointly with a team of the V.E. Zuev Institute of Atmospheric Optics of the Siberian Branch of the Russian Academy of Sciences have discovered a method to increase the operation range of optical traps also known
Optical tweezers are a device which uses a laser beam to move micron-sized objects such as living cells, proteins, and molecules. In 2018, the American...
23.07.2020 | Event News
21.07.2020 | Event News
07.07.2020 | Event News
03.08.2020 | Information Technology
03.08.2020 | Information Technology
03.08.2020 | Life Sciences