Discovery of 33mer in chromosome 21 – the largest alpha satellite higher order repeat unit among all human somatic chromosomes

Scientific paper - Original scientific paper

• Author: Matko Glunčić
• Author: Ines Vlahović
• Author: Vladimir Paar
• Author's institution: University of Zagreb; Faculty of Science; (Department of Physics)
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Physics
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Interdisciplinary Natural Sciences
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Computing
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract (english)

The centromere is important for segregation of chromosomes during cell division in eukaryotes. Its destabilization results in chromosomal missegregation, aneuploidy, hallmarks of cancers and birth defects. In primate genomes centromeres contain tandem repeats of ~171 bp alpha satellite DNA, commonly organized into higher order repeats (HORs). In spite of crucial importance, satellites have been understudied because of gaps in sequencing - genomic “black holes”. Bioinformatical studies of genomic sequences open possibilities to revolutionize understanding of repetitive DNA datasets. Here, using robust (Global Repeat Map) algorithm we identified in hg38 sequence of human chromosome 21 complete ensemble of alpha satellite HORs with six long repeat units (≥20 mers), five of them novel. Novel 33mer HOR has the longest HOR unit identified so far among all somatic chromosomes and novel 23mer reverse HOR is distant far from the centromere. Also, we discovered that for hg38 assembly the 33mer sequences in chromosomes 21, 13, 14, and 22 are 100% identical but nearby gaps are present ; that seems to require an additional more precise sequencing. Chromosome 21 is of significant interest for deciphering the molecular base of Down syndrome and of aneuploidies in general. Since the chromosome identifier probes are largely based on the detection of higher order alpha satellite repeats, distinctions between alpha satellite HORs in chromosomes 21 and 13 here identified might lead to a unique chromosome 21 probe in molecular cytogenetics, which would find utility in diagnostics. It is expected that its complete sequence analysis will have profound implications for understanding pathogenesis of diseases and development of new therapeutic approaches.

• Keywords (english): human genome; alpha satellite; higher order repeats; GRM; chromosome 21
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review - international
• Publication version: Published version
• Journal title: Scientific Reports
• Numbering: vol. 9, 12629
• p-ISSN: 2045-2322
• DOI: https://doi.org/10.1038/s41598-019-49022-2
• URN:NBN: urn:nbn:hr:217:907668
• Publication: 2019
• Document URL: https://www.nature.com/articles/s41598-019-49022-2
• Type of resource: Text
• Access conditions: Open access
• Public note: © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-019-49022-2. Received: 25 January 2019. Accepted: 13 August 2019. Published online: 02 September 2019.
• Created on: 2020-08-26 19:04:03