Paul-Flechsig-Institut für Hirnforschung
 Universitätsmedizin Leipzig

Single cell genomics of the brain in healthy controls and disease

We recently described chromosomal copy number variation (CHROM-CNV) due to loss or gain of whole chromosomes or fragments thereof both in the normal and diseased adult human brain, namely Alzheimer´s disease (AD). In sporadic AD, we observed accelerated cell death for neurons with CHROM-CNV. This indicates that maintenance of neurons with CHROM-CNV in the adult CNS might be a widespread phenomenon. While during development, neurons with CHROM-CNV might be cleared through apoptosis, certain neurons still may escape this selection and persist into adulthood.

In the adult brain, Neurons with CHROM-CNV might be subjected to delayed apoptosis, causing late-onset degenerative disease. As different types of CHROM-CNV may relate to an uneven apoptotic potential, each type of chromosome complement abnormality might possess a different propensity for apoptotic clearance. To understand the genetic background for neuronal diversity in the normal brain and for impaired viability in AD, it will be essential to determine the overall rate of CHROM-CNV for the full complement of chromosomes. It thus will be the aim of the project to analyze the prevalence of CHROM-CNV in the adult normal human brain and in AD with respect to its overall frequency, regional distribution and type of chromosome complement involved. To this end, groups in Russia, Germany, Turkey and France will jointly apply a strategy that combines high throughput screening for neuronal CHROM-CNV by slide-based cytometry with in depth analysis by chromosomal multi-colour-interphase FISH and interphase chromosome-specific multi-colour banding. Herewith we will make a first step towards the long-term goal of therapeutic interference with the epigenetic machinery to restore cell states caused by CHROM-CNV.

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ERA Net RUS Plus "Significans"

 
last update: 12.06.2018, 13:52 Uhr
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Paul-Flechsig-Institut für Hirnforschung