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A three-letter sequence repeating along a stretch of DNA could offer new clues about why some people are more susceptible to Alzheimer's disease than others. The sequence, CCG, sits in a region of DNA that controls the gene FAM193B.

Researchers at the Hong Kong University of Science and Technology and other institutions recently explored the possibility that differences in this sequence's repetition are associated with Alzheimer's disease. Their study, published in Nature Neuroscience, linked longer repeats to higher odds of having the disease in Chinese participants, with a smaller association in people of European ancestry.

Laboratory experiments also suggested that longer repeats increase FAM193B activity, hinting at a possible link between this inherited DNA variation and processes involved in cellular damage.

Many studies exploring the underpinnings of genetic susceptibility to specific diseases or disorders focus on variations at individual positions in DNA, whose four chemical bases are represented by the letters A, T, C and G. However, DNA can also present other variations, including inserted, deleted or repeated letter sequences. The researchers wanted to determine whether these structural differences could be linked to different levels of susceptibility to Alzheimer's.

Repeated sequences are difficult to reconstruct, especially when DNA sequencing machines read genetic material in short fragments. To address this problem, the researchers used longer DNA readings from 11 Chinese individuals to build a reference set of structural variants, then analyzed larger collections of short readings.

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