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1.
PLoS One ; 10(2): e0117854, 2015.
Article in English | MEDLINE | ID: mdl-25689626

ABSTRACT

Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.


Subject(s)
Dentate Gyrus/physiology , Long Interspersed Nucleotide Elements/physiology , Neurogenesis/genetics , Neurons/physiology , Brain/physiology , Genome, Human , Humans , Promoter Regions, Genetic
2.
Proc Natl Acad Sci U S A ; 111(16): 5980-5, 2014 Apr 22.
Article in English | MEDLINE | ID: mdl-24711416

ABSTRACT

Adaptive immunity in humans is provided by hypervariable Ig-like molecules on the surface of B and T cells. The final set of these molecules in each organism is formed under the influence of two forces: individual genetic traits and the environment, which includes the diverse spectra of alien and self-antigens. Here we assess the impact of individual genetic factors on the formation of the adaptive immunity by analyzing the T-cell receptor (TCR) repertoires of three pairs of monozygous twins by next-generation sequencing. Surprisingly, we found that an overlap between the TCR repertoires of monozygous twins is similar to an overlap between the TCR repertoires of nonrelated individuals. However, the number of identical complementary determining region 3 sequences in two individuals is significantly increased for twin pairs in the fraction of highly abundant TCR molecules, which is enriched by the antigen-experienced T cells. We found that the initial recruitment of particular TCR V genes for recombination and subsequent selection in the thymus is strictly determined by individual genetic factors. J genes of TCRs are selected randomly for recombination; however, the subsequent selection in the thymus gives preference to some α but not ß J segments. These findings provide a deeper insight into the mechanism of TCR repertoire generation.


Subject(s)
High-Throughput Nucleotide Sequencing , Receptors, Antigen, T-Cell/genetics , Twins, Monozygotic/genetics , Clone Cells , Complementarity Determining Regions/genetics , Female , Gene Library , Genetic Variation , Humans , Sequence Analysis, DNA , T-Lymphocytes/metabolism , Thymus Gland/metabolism
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