Rapid molecular assays to study human centromere genomics
- Rafael Contreras-Galindo1,
- Sabrina Fischer1,2,
- Anjan K. Saha1,3,4,
- John D. Lundy1,
- Patrick W. Cervantes1,
- Mohamad Mourad1,
- Claire Wang1,
- Brian Qian1,
- Manhong Dai5,
- Fan Meng5,6,
- Arul Chinnaiyan7,8,
- Gilbert S. Omenn1,9,10,
- Mark H. Kaplan1 and
- David M. Markovitz1,4,11,12
- 1Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 2Laboratory of Molecular Virology, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay 11400;
- 3Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 4Program in Cancer Biology, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 5Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 6Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 7Michigan Center for Translational Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;
- 8Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA;
- 9Department of Human Genetics,
- 10Departments of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 11Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA;
- 12Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
Abstract
The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere genomics in biology are laborious. We have identified specific markers in the centromere of 23 of the 24 human chromosomes that allow for rapid PCR assays capable of capturing the genomic landscape of human centromeres at a given time. Use of this genetic strategy can also delineate which specific centromere arrays in each chromosome drive the recruitment of epigenetic modulators. We further show that, surprisingly, loss and rearrangement of DNA in centromere 21 is associated with trisomy 21. This new approach can thus be used to rapidly take a snapshot of the genetics and epigenetics of each specific human centromere in nondisjunction disorders and other biological settings.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.219709.116.
- Received December 14, 2016.
- Accepted October 27, 2017.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
