Inverted Duplications on Acentric Markers: Mechanism of Formation

Overview

Journal Hum Mol Genet

Specialties Genetics
Molecular Biology

Date 2009 Apr 2

PMID 19336476

Citations 18

Authors

Andrea E Murmann

Donald F Conrad

Heather Mashek

Chris A Curtis

Raluca I Nicolae

Carole Ober

Stuart Schwartz

Affiliations

Soon will be listed here.

Abstract

Acentric inverted duplication (inv dup) markers, the largest group of chromosomal abnormalities with neocentromere formation, are found in patients both with idiopathic mental retardation and with cancer. The mechanism of their formation has been investigated by analyzing the breakpoints and the genotypes of 12 inv dup marker cases (three trisomic, six tetrasomic, two polysomic and one X chromosome derived marker) using a combination of fluorescence in situ hybridization, quantitative SNP array and microsatellite analysis. Inv dup markers were found to form either symmetrically with one breakpoint or asymmetrically with two distinct breakpoints. Genotype analyses revealed that all inv dup markers formed from one single chromatid end. This observation is incompatible with the previously suggested model by which the acentric inv dup markers form through inter-chromosomal U-type exchange. On the basis of the identification of DNA sequence motifs with inverted homologies within all observed breakpoint regions, a new general mechanism is proposed for the acentric inv dup marker formation: following a double-strand break an acentric fragment forms, during either meiosis or mitosis. The open DNA end of the acentric fragment is stabilized by the formation of an intra-chromosomal loop promoted by the presence of sequences with inverted homologies. Likely coinciding with the neocentromere formation, this stabilized fragment is duplicated during an early mitotic event, insuring the marker's survival during cell division and its presence in all cells.

Citing Articles

Identification of small-sized intrachromosomal segments at the ends of INV-DUP-DEL patterns.

Shimojima Yamamoto K, Tamura T, Okamoto N, Nishi E, Noguchi A, Takahashi I J Hum Genet. 2023; 68(11):751-757.

PMID: 37423943 DOI: 10.1038/s10038-023-01181-x.

Case Report: Prenatal Identification of a Mosaic Neocentric Marker Resulting in 13q31.1→qter Tetrasomy in a Mildly Affected Girl.

Dharmadhikari A, Pereira E, Andrews C, Macera M, Harkavy N, Wapner R Front Genet. 2022; 13:906077.

PMID: 35928455 PMC: 9343796. DOI: 10.3389/fgene.2022.906077.

The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA.

Barra V, Fachinetti D Nat Commun. 2018; 9(1):4340.

PMID: 30337534 PMC: 6194107. DOI: 10.1038/s41467-018-06545-y.

Sequence Composition and Evolution of Mammalian B Chromosomes.

Rubtsov N, Borisov Y Genes (Basel). 2018; 9(10).

PMID: 30309007 PMC: 6211034. DOI: 10.3390/genes9100490.

A boy with developmental delay and mosaic supernumerary inv dup(5)(p15.33p15.1) leading to distal 5p tetrasomy - case report and review of the literature.

Tesner P, Drabova J, Stolfa M, Kudr M, Kyncl M, Moslerova V Mol Cytogenet. 2018; 11:29.

PMID: 29760779 PMC: 5941596. DOI: 10.1186/s13039-018-0377-1.

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