Researchers look for answers regarding tiny changes in how the brain works

Researchers at Yale University led by doctoral student Michelle Renfrew studied three genetically distinct populations — Yebo, Africa; Scmeliana, Indiana; and Capilano, British Columbia — in an effort to understand the implications of two known changes in the structure of mammalian neuronal DNA. The changes both involve stretches of nucleotides, which are typically used to package and group different types of information (e.g., protein bound to amino acids).

Within the Scmeliana group, for example, some stretches of DNA — O.glut3q is one of them — in which one amino acid (like glutamic acid) is bound together with another (like in glutamine) have switched to a different formation of nucleotides, and altered the way glutamate attaches to amino acids. Yale scientists also determined the extent to which the H8, H10, and K4 protein binding proteins in the group are different (K4, for example, has shifted into a different binding protein type than in Scmeliana.)

On the other hand, in the other location studied, there was no change in nucleotides, but instead some noticeable changes in the formation of K4 binding proteins and glutamine binding proteins. However, a larger sequence on the Yebo and Capilano groups matched those shown by the K4 and H8 proteins, and their two H8-binding proteins also had some strange alterations.

“We saw that the nucleotide sequences (a.k.a. the genes) differed quite a bit from one population to the next, with smaller differences in some of the cases and a large difference in the cases of H4 and K8,” Renfrew said. This suggests that some of these H8-binding proteins are new proteins created by H8 proteins switching to a different amino acid pair (e.g., glutamic acid-binding as opposed to glutamine-binding as in some previous research). In other research, scientists have seen that these different gene sequences play a role in causing disease — in at least one population, Alzheimer’s disease.

Whether mutations in glutamate receptors are contributing to this rare form of Alzheimer’s, Renfrew said, is “an open question,” and that she still needs to conduct additional research to prove it.

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