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Centromeres in Health, Disease and Evolution

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Genomic Elements in Health, Disease and Evolution

Abstract

The centromere is a protein–DNA structure that is essential for the correct segregation of chromosomes to daughter cells. In human cells it is located at a specific region of each chromosome that is devoid of genes and characterized by heterochromatin. The underlying DNA is made up of a 171-bp tandem repeat known as alpha satellite, which is organized in a head-to-tail arrangement and spans up to several megabases in length. The centromere DNA is the foundation onto which over 100 proteins form a structure known as the kinetochore. This structure fully assembles during mitosis and is instrumental in the capture of spindle microtubules and the movement of chromosomes to opposing poles of the cell. In this chapter we describe the main cellular functions of the centromere in a healthy cell and show how errors in its normal role can contribute to human diseases such as developmental disorders, cancer, infertility and premature aging. In addition, we examine the evolution of centromere DNA and proteins in humans and primates and the emergence of new centromeres in non-satellite DNA locations.

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Abbreviations

ANIFAD:

Associated network instability, and facial anomalies division

ALP-WDLPS:

Atypical lipomas and well-differentiated liposarcomas

AML:

Acute myeloid leukemia

ATLL:

Adult T-cell leukemia/lymphoma

CCAN:

Constitutive centromere -associated network

CENP:

Centromere protein

CGI:

CpG island

CIN:

Chromosomal instability

CLL:

Chronic lymphocytic leukemia

CPC:

Chromosome passenger complex

FISH:

Fluorescence in situ hybridization

HOR:

Higher order repeat

ICF:

Immunodeficiency, centromeric instability, and facial anomalies

MVA:

Mosaic variegated aneuploidy

PCD:

Premature centromere division

PCS:

Premature chromatid separation

ROB:

Robertsonian translocation

SAC:

Spindle assembly checkpoint

TE:

Transposable element

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Authors and Affiliations

  1. Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, VIC, 3052, Australia

    Thian Thian Beh B.Sc. & Paul Kalitsis Ph.D.

  2. Department of Paediatrics, University of Melbourne, Melbourne, VIC, 3052, Australia

    Thian Thian Beh B.Sc. & Paul Kalitsis Ph.D.

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  1. Thian Thian Beh B.Sc.
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  2. Paul Kalitsis Ph.D.
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Correspondence to Paul Kalitsis Ph.D. .

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  1. Department of Life and Health Sciences and University of Nicosia Medical School, University of Nicosia, Nicosia, Cyprus

    Kyriacos Felekkis

  2. Department of Biological Sciences, Molecular Medicine Research Center, University of Cyprus, Nicosia, Cyprus

    Konstantinos Voskarides

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Beh, T.T., Kalitsis, P. (2015). Centromeres in Health, Disease and Evolution. In: Felekkis, K., Voskarides, K. (eds) Genomic Elements in Health, Disease and Evolution. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3070-8_9

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