Ramos S, Molina B, Grether P, Mayén DG, Castro O, Ángeles M, Rodríguez R, Frías S

Language: Spanish
References: 14
Page: 374-382
PDF size: 518.77 Kb.

ABSTRACT

Chromosomal heteromorphisms are normal variants, considered without phenotypic impact, some of the most frequent are in the short arms of the acrocentric chromosomes (13, 14, 15, 21, 22). Recently it has been suggested that a type of chromosomal rearrangements considered heteromorphisms, known as cryptic translocation of acrocentric chromosomes (TCA), may be an etiological factor of numerical chromosomal abnormalities or aneuploidies, which are aborted by 90%.
Objective: To determine the frequency of TCAs in a group of 62 spontaneous abortions presenting an aneuploidy of acrocentric chromosomes.
Material and methods: 50 healthy individuals and 62 abortions with aneuploidy of any of the acrocentric chromosomes were included: nine trisomy 13, seven trisomy 14, eleven trisomy 15, nineteen trisomy 21 and sixteen trisomy 22. G-banded karyotype was performed to detect the aneuploidy and we used fluorescence in situ hybridization with probe D13Z1/D21Z1, D14Z1/D22Z1 and D15Z1 in order to study TCA, 15-20 metaphases were examined under an epifluorescence microscope.
Results: 14% TCAs were observed in healthy individuals and 17.7% in abortions, without significant difference. In all cases the region D15Z1 was involved in the rearrangement, mainly translocated from short arms of chromosome 15 to the short arm of chromosome 13 or 14.
Conclusions. The TCAs involving the region D15Z1 are a normal variant, with a high frequency in the sample of the Mexican population studied; this variant appears not to be involved in the etiology of acrocentric aneuploidy. Our findings suggest that this heteromorphism is a translocation or non-homologous recombination between acrocentric chromosomes involving D15Z1 region, and its frequency varies among ethnic groups.

REFERENCES

1. Hassold T, Hall H, Hunt P. The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet 2007;16:203-208.

2. Nagaoka SI, Hassold TJ, Hunt PA. Human aneuploidy: mechanisms and new insights into an age-old problem. Nature Rev Genetics 2012;13:493-504.

3. Gregan J, Polakova S, Zhang L, Tolić-Nørrelykke IM, Cimini D. Merotelic kinetochore attachment: causes and effects. Trends Cell Biol 2011;21:374–381.

4. Storchova Z. The Causes and Consequences of Aneuploidy in Eukaryotic Cells. En: Aneuploidy in Health and Disease, Storchova Z (Ed.), 2012, ISBN: 978-953-51-0608-1, InTech, Disponible en: http://www.intechopen.com/books/aneuploidy-in-health-and-disease/the-effect-of-aneuploidy-onphysiology-of- eukaryotic-cell

5. Craig-Holmes AP, Moore FB, Shaw MW. Polymorphism of Human C-Band Heterochromatin. II. Family Studies with Suggestive Evidence for Somatic Crossing Over. Am J Hum Genet 1975;27:178-189.

6. Rozés G. Human centromeric alphoid domains are periodically homogenized so that they vary substantially between homologues. Mechanism and implications for centromere functioning. Nucleic Acids Res 2006;34(6):1912-1924.

7. Jarmuz M, Glotzbach CD, Bailey KA, Bandyopadhyay R, Shaffer LG. The evolution of satellite III DNA subfamilies among primates. Am J Hum Genet 2007;80:495-501.

8. Cockwell AE, Jacobs PA, Beal SJ, Crolla JA. A study of cryptic terminal chromosome rearrangements in recurrent miscarriage couples detects unsuspected acrocentric pericentromeric abnormalities. Hum Genet 2003;112:298-302.

9. Ramos S, Alcántara MA, Molina B, Del Castillo V, Sánchez S, Frias S. Acrocentric cryptic translocation associated with nondisjunction of chromosome 21. Am J Med Genet 2008;146A:97-102.

10. Smeets DFCM, Merkx GFM, Hopman AHM. Frequent occurrence of translocations of the short arm of chromosome 15 to other D-group chromosomes. Hum Genet 1991;87:45-48.

11. Higgins MJ, Wang H, Shtromas I, Haliotis T, Roder JC, Holden JJA, White BN. Organization of a repetitive human 1.8 kb KpnI sequence localized in the heterochromatin of chromosome 15. Chromosoma (Berl) 1985;93:77-86.

12. Stergianou K, Gould CP, Waters JJ, Hultén M. High population incidence of the 15p marker D15Z1 mapping to the short arm of one homologue 14. Hum Genet 1992;88:364.

13. Stergianou K, Gould CP, Waters JJ, Hultén MA. A DA/DAPI positive human 14p heteromorphism defined by fluorescence in-situ hybridization using chromosome 15-specific probes D15Z1 (satellite II) and p-TRA-25 (alphoid). Hereditas 1993;119:105-110.

14. Cockwell AE, Jacobs PA, Crolla JA. Distribution of the D15Z1 copy number polymorphism. Eur J Hum Genet 2007;15:441-445.