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Related Concept Videos

Genomic DNA in Eukaryotes00:58

Genomic DNA in Eukaryotes

Eukaryotes have large genomes compared to prokaryotes. To fit their genomes into a cell, eukaryotic DNA is packaged extraordinarily tightly inside the nucleus. To achieve this, DNA is tightly wound around proteins called histones, which are packaged into nucleosomes that are joined by linker DNA and coil into chromatin fibers. Additional fibrous proteins further compact the chromatin, which is recognizable as chromosomes during certain phases of cell division.
DNA Packaging00:58

DNA Packaging

Overview
Chromatin Packaging02:21

Chromatin Packaging

Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter? 
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Chromatin Packaging01:32

Chromatin Packaging

Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
Genetic Material01:20

Genetic Material

Within the human body, a complex and detailed system of trillions of cells works in unison to sustain life. Each cell houses a nucleus, which contains 46 chromosomes divided into 23 pairs. Chromosomes are highly coiled structures made of the genetic material DNA. These chromosomes are essential carriers of genetic information, with half inherited from the mother through her egg and the other half from the father's sperm, combining to create the unique genetic makeup of an individual.

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DNA Methylation: Bisulphite Modification and Analysis
12:34

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Quantifying the proportion of different cell types in the human cortex using DNA methylation profiles.

Eilis Hannon1, Emma L Dempster2, Jonathan P Davies2

  • 1Department of Clinical and Biomedical Sciences, University of Exeter Medical School, University of Exeter, Barrack Road, RILD Building, Royal Devon & Exeter Hospital, Barrack Road, Exeter, Devon, EX2 5DW, UK. E.J.Hannon@exeter.ac.uk.

BMC Biology
|January 25, 2024
PubMed
Summary

New computational models accurately estimate human cortex cell proportions using DNA methylation data. Glial cells are twice as abundant as neuronal cells, with specific cell type proportions linked to Alzheimer's disease neuropathology.

Keywords:
Alzheimer’s diseaseBrainCellular heterogeneityDNA methylationGliaNeurons

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Area of Science:

  • Neuroscience
  • Genetics
  • Epigenetics

Background:

  • Human cortex cellular composition varies between individuals, necessitating covariate inclusion in epigenome-wide association studies (EWAS) using bulk tissue.
  • Computational methods estimating cell proportions from DNA methylation data are crucial due to the frequent unavailability of experimental cell counts.

Purpose of the Study:

  • To validate and profile an expanded reference DNA methylation dataset for quantifying human cortex cellular composition.
  • To assess the performance of novel deconvolution models incorporating neuronal and glial cell subtypes.

Main Methods:

  • Tested eight reference panels with varying neuronal and glial cell type combinations.
  • Characterized deconvolution performance using computationally reconstructed and empirically derived human cortex DNA methylation data.

Main Results:

  • Novel brain deconvolution models accurately estimate cellular proportions in postnatal human cortex samples but not in prenatal cortex or cerebellum.
  • Glial cells are twice as abundant as neuronal cells in the human cortex.
  • Significant associations were found between Alzheimer's disease neuropathology and specific cell type proportions, including decreased NeuNNeg/SOX10Neg and increased NeuNNeg/SOX10Pos nuclei.

Conclusions:

  • Novel deconvolution models provide accurate cell proportion estimates for the human cortex.
  • These models serve as a community resource to control for cellular heterogeneity in epigenetic studies of brain disorders using bulk cortex tissue.