University of California University in San Diego created the most complete atlas of chromosomal sites, which are potentially connected with the inheritance of complex character traits or the development of diseases. These “hot spots” enhance the activity of genes underlying such disorders as diabetes, Alzheimer’s disease or autoimmune violations. The results of the study are published in Cell magazine.
In the human body there are many different types of cells (nervous, muscle, fatty, etc.), which have the same DNA set. The type of cell depends on which genes are active in it, and which are suppressed. It is known that this is controlled by special regulators, such as promoters and enhancers. They are DNA sections on the same chromosome as the gene regulated by them (therefore they are called cis-regulatory elements or CCREs). Current catalogs of human regulatory sequences are still incomplete, although scientists suggest that many of these elements may be associated with diseases.
Scientists analyzed 615,998 cell nuclei of 30 types of human tissues obtained from several adult donors to form an open chromatin profile – sections of chromosomes, which are involved in interactions with other biological molecules, for example, with transcription factors, which in turn affects the activity of genes. Experts found 890,130 areas of open chromatin corresponding to CCRE.
The data obtained researchers have combined with the results of the previous study, in which the areas of open chromatin were determined for cells of 15 types of tissues of human embryos. This made it possible to trace how chromatine profiles change throughout the human life. In general, scientists have identified profiles for 1.3 million cells and made up cards for 1.15 million cis regulatory sequences covering 14.8 percent of the genome in 222 cell types.
The command used the CCRE atlas compiled by it in order to associate certain genetic options with complex human features or diseases. For example, researchers revealed a variant of the RS16940186 gene, which is greatest likely associated with ulcerative colitis. This option enhances the expression of the IRF8 molecule in the epithelial cells of the gastrointestinal tract through the creation of an open chromatin in the place where an enhancer is connected to transcription factors. This confirms that the Atlas is useful for identifying molecular mechanisms of various genetic disorders.