Novel Concept of Alpha Satellite Cascading Higher-Order Repeats (HORs) and Precise Identification of 15mer and 20mer Cascading HORs in Complete T2T-CHM13 Assembly of Human Chromosome 15

Scientific paper - Original scientific paper

• Author: Matko Glunčić
• Author: Ines Vlahović
• Author: Marija Rosandić
• 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: INTERDISCIPLINARY AREAS OF KNOWLEDGE; Biotechnology in Biomedicine (natural science, biomedicine and healthcare, bioethics area

Abstract (english)

Unraveling the intricate centromere structure of human chromosomes holds profound implications, illuminating fundamental genetic mechanisms and potentially advancing our comprehension of genetic disorders and therapeutic interventions. This study rigorously identified and structurally analyzed alpha satellite higher-order repeats (HORs) within the centromere of human chromosome 15 in the complete T2T-CHM13 assembly using the high-precision GRM2023 algorithm. The most extensive alpha satellite HOR array in chromosome 15 reveals a novel cascading HOR, housing 429 15mer HOR copies, containing 4-, 7- and 11-monomer subfragments. Within each row of cascading HORs, all alpha satellite monomers are of distinct types, as in regular Willard’s HORs. However, different HOR copies within the same cascading 15mer HOR contain more than one monomer of the same type. Each canonical 15mer HOR copy comprises 15 monomers belonging to only 9 different monomer types. Notably, 65% of the 429 15mer cascading HOR copies exhibit canonical structures, while 35% display variant configurations. Identified as the second most extensive alpha satellite HOR, another novel cascading HOR within human chromosome 15 encompasses 164 20mer HOR copies, each featuring two subfragments. Moreover, a distinct pattern emerges as interspersed 25mer/26mer structures differing from regular Willard’s HORs and giving rise to a 34-monomer subfragment. Only a minor 18mer HOR array of 12 HOR copies is of the regular Willard’s type. These revelations highlight the complexity within the chromosome 15 centromeric region, accentuating deviations from anticipated highly regular patterns and hinting at profound information encoding and functional potential within the human centromere.

• Keywords (english): T2T-CHM13 human assembly; alpha satellites; higher-order repeats; centromere; GRM algorithm
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review - international
• Publication version: Published version
• Journal title: International Journal of Molecular Sciences
• Numbering: vol. 25, no. 8, 4395
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms25084395
• URN:NBN: urn:nbn:hr:217:391449
• Publication: 2024-04-16
• Project: Number: IP-2019-04-2757; Title (croatian): Varijante u repetitivnim strukturama višeg reda u centromernim i NBPF dijelovima genoma čovjeka i viših primata; Title (english): Variants in higher order repeat structures in centromeric and NBPF regions of human and higher primates genomes; Acronym: HORVAR; Leader: Matko Glunčić; Jurisdiction: Croatia; Funding stream: Research Projects
• Document URL: https://www.mdpi.com/1422-0067/25/8/4395
• Type of resource: Text
• Access conditions: Open access
• Public note: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Received: 6 March 2024. Revised: 8 April 2024. Accepted: 11 April 2024. Published: 16 April 2024.
• Created on: 2024-07-24 10:24:19