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> Everyone's DNA has a variety of differing enhancers that make each of us different:
> 
> https://medicalxpress.com/news/2020-12-vary-biologically.html
> 
> "Genetics has made huge strides over the past 20 years, from the sequencing of the human genome to a growing understanding of factors that turn genes on and off, namely transcription factors and the DNA "enhancer" sequences they bind to. New research from Boston Children's Hospital introduces another previously unknown layer of human genetics. It finds genetic variation in a gene's ability to react to chemical signals from the outside.
> 
> ***
> 
> "'We found that human genetics determine, on a gene to gene basis, whether a cell will respond to an outside signal," says Zon, who is also affiliated with Dana-Farber/Boston Children's Cancer and Blood Disorders Center, the Howard Hughes Medical Institute, and the Harvard Stem Cell Institute. "We believe that many genetic conditions are due to a defect in this response—a 'signalopathy.'"
> 
> ***
> 
> "As it turns out, many variants tied to these traits mapped to a small subset of gene enhancers. These enhancers bind to two types of gene regulators: master transcription factors that regulate which type of blood cell is being made, and signaling transcription factors that coordinate responses to signals from outside the cell.
> 
> "When Zon and colleagues looked at blood cell progenitors in the lab, they found that many of the variants altered the DNA sequences of enhancers to which signaling transcription factors bind. This, they showed, prevented the factors from binding to the enhancer. That missed signal prevented adjacent genes from turning on—genes that normally would turn on in response to cues driving red blood cell maturation.
> 
> ***
> 
> "GWAS studies have mapped many traits to variations in DNA enhancer sequences. But no one had ever shown that traits can be altered because of a failure of signals to get through.
> 
> "'This wasn't known before," says Zon. "If we want to better understand human variation, we have to find those regions in the genome, in every tissue, that are receiving transcriptional signals from outside the cell. People vary in how much signaling can happen in an individual gene.'"
> 
> Comment: Most of the DNA active in these processes is not in the coding areas and shows that non-coding areas are vital to functions. 3-D  relationships are extremely important.