Genomic Diversity in the Human Brain: the Functional Role of Expandable DNA Repeats

神经细胞在发育和成年过程中积累遗传变化，最近的证据表明，由此产生的基因组多样性可能是神经元功能多样性的基础。迄今为止，只有几种类型的体细胞遗传变异在人类大脑中被表征出来。三核苷酸重复序列（trucleotide repeats， TNR）是基因组不稳定的热点，TNR在特定位点的扩增会导致数十种脑部疾病，这表明人类大脑特别容易受到这种遗传变异的影响。该项目旨在首次在全基因组范围内研究人类大脑TNR体细胞不稳定性，从而从一个新颖且高度相关的角度解决大脑的遗传多样性问题。

Neuronal cells accumulate genetic changes during development and adult life, and recent evidence suggests that the resulting genomic diversity may underlie neuronal functional diversity. To date only a few types of somatic genetic variation have been characterised in the human brain. Trinucleotide repeats (TNR) are hotspots of genomic instability and TNR expansions at specific loci cause dozens of brain disorders, suggesting that the human brain is particularly vulnerable to this type of genetic variation. This project aims to investigate, for the first time, TNR somatic instability in the human brain on a genome-wide scale, therefore, addressing the genetic diversity of the brain from a novel and highly relevant angle.