5:42 am - Thursday December 14, 2017

Genetic causes of common disorders revealed

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Washington – Researchers have found that six common diseases arise from DNA changes located outside genes.

The study from the laboratory of Peter Scacheri, PhD, shows that multiple DNA changes, or variants, work in concert to affect genes, leading to autoimmune diseases including rheumatoid arthritis, Crohn’s disease, celiac disease, multiple sclerosis, lupus and colitis.

Further, for each disease, multiple different genes are manipulated by several small differences in DNA.
Scacheri, associate professor of genetics and genome sciences, said that they’ve known that rare diseases are due to one change within one gene with major effects, asserting that the key take away is that common diseases are due to many changes with small effects on a handful of genes.

The human genome includes 3 billion letters of DNA. Only 1 to 2 percent of the letters are used as the blueprint for proteins, the body’s building blocks. Scacheri’s team is part of group of scientists investigating where and why DNA goes awry in the remaining 98 percent – the regions between genes.

These regions contain thousands of genetic switches that control the levels of genes. This new finding shows that in common diseases, the fine-tuning of those switches is not quite right, leading to incorrect expression of some key genes – previously unidentified.

The Scacheri lab’s study provides a new model for understanding how genetic variants explain variation in common, complex diseases such as rheumatoid arthritis and colitis. That is, the effect of an individual variant may be very small, but when coupled with other nearby variants, the manifestations are much greater, said Anthony Wynshaw-Boris, MD, PhD, chair of the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine.

The study has been published online in the journal Genome Research.

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