Rapid molecular assays to study human centromere genomics

Rafael Contreras-Galindo, Sabrina Fischer, Anjan K. Saha, John D. Lundy, Patrick W. Cervantes, Mohamad Mourad, Claire Wang, Brian Qian, Manhong Dai, Fan Meng, Arul Chinnaiyan, Gilbert S. Omenn, Mark H. Kaplan, David M. Markovitz

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 nondis-junction disorders and other biological settings.

Original languageEnglish (US)
Pages (from-to)2040-2049
Number of pages10
JournalGenome research
Volume27
Issue number12
DOIs
StatePublished - Dec 2017

Bibliographical note

Funding Information:
The authors thank Joseph Zahn for help in preparing this manuscript and Ting Wu for very helpful suggestions. This work was supported by grant K22 CA177824 from the National Cancer Institute to R.C.-G.; grant 05–5089 from the Concerned Parents for AIDS Research CPFA to M.H.K.; and by grant R01 CA144043 from the National Institutes of Health (NIH) to D.M.M. S.F. was supported by the fellowship MOV_CA_2013_1_10789 from the Programa de Desarrollo de Ciencias Básicas (PEDECIBA), Agencia Nacional de Investigación e Innovación (ANII) from the Uruguayan government. M.M. was supported by the University of Michigan Undergraduate Research Opportunity Program (UROP). A.K.S. was supported by a University of Michigan Cancer Biology Program Fellowship and the Medical Science Training Program (MSTP). P.W.C. was supported by NIH Postbaccalaureate Research Education Program (PREP) grant R25GM086262-07. G.S.O. acknowledges support from NIH grants RM-08-029 and P30U54ES017885.

Funding Information:
The authors thank Joseph Zahn for help in preparing this manuscript and Ting Wu for very helpful suggestions. This work was supported by grant K22 CA177824 from the National Cancer Institute to R.C.-G.; grant 05-5089 from the Concerned Parents for AIDS Research CPFA to M.H.K.; and by grant R01 CA144043 from the National Institutes of Health (NIH) to D.M.M. S.F. was supported by the fellowship MOV_CA_2013_1_10789 from the Programa de Desarrollo de Ciencias Básicas (PEDECIBA), Agencia Nacional de Investigación e Innovación (ANII) from the Uruguayan government. M.M. was supported by the University of Michigan Undergraduate Research Opportunity Program (UROP). A.K.S. was supported by a University of Michigan Cancer Biology Program Fellowship and the Medical Science Training Program (MSTP). P.W.C. was supported by NIH Postbaccalaureate Research Education Program (PREP) grant R25GM086262-07. G.S.O. acknowledges support from NIH grants RM-08-029 and P30U54ES017885.

Publisher Copyright:
© 2017 Contreras-Galindo et al.

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