Satellite DNAs and human sex chromosome variation

Abstract

Satellite DNAs are present on every chromosome in the cell and are typically enriched in repetitive, heterochromatic parts of the human genome. Sex chromosomes represent a unique genomic and epigenetic context. In this review, we first report what is known about satellite DNA biology on human X and Y chromosomes, including repeat content and organization, as well as satellite variation in typical euploid individuals. Then, we review sex chromosome aneuploidies that are among the most common types of aneuploidies in the general population, and are better tolerated than autosomal aneuploidies. This is demonstrated also by the fact that aging is associated with the loss of the X, and especially the Y chromosome. In addition, supernumerary sex chromosomes enable us to study general processes in a cell, such as analyzing heterochromatin dosage (i.e. additional Barr bodies and long heterochromatin arrays on Yq) and their downstream consequences. Finally, genomic and epigenetic organization and regulation of satellite DNA could influence chromosome stability and lead to aneuploidy. In this review, we argue that the complete annotation of satellite DNA on sex chromosomes in human, and especially in centromeric regions, will aid in explaining the prevalence and the consequences of sex chromosome aneuploidies.

Keywords: Aneuploidy; Centromere; Satellite DNA; Sex chromosomes; X-inactivation.

Fig. 1.

Repeats that involve satellite DNA on human sex chromosomes. Satellites on the human X and Y chromosomes are plotted along these chromosomes. The locations of many satellites discussed in Section 2 are depicted, most prominently DXZ and DYZ arrays, as well as HSAT. The human Y chromosome has the shortest centromere in the human genome and no CENP-B box. Figure created with BioRender.com.

Fig. 2.

Factors influencing the variation in satellite arrays and the possible consequences of such variability. The specific underlying sequence, such as individual variants of HORs, cenhaps, epigenetics, and the chromatin organization are all possible contributors to the variation in satellites. This might in turn have consequences for human aneuploidies, and especially sex chromosome aneuploidies. These include those that arise in early development, such as Turner syndrome, Trisomy X, Klinefelter syndrome, or Jacobs syndrome, and those that arise later in life and are linked to aging, such as loss of X and Y chromosomes. Figure created with BioRender.com.

Fig. 3.

Challenges when analyzing satellite DNA with NGS. (A) The challenges are either inherent (e.g. long unit sizes of repeats or repeat arrays spanning hundreds of kbs) or technological (e.g. algorithms that inadequately assess homopolymer lengths). (B) Repeats and their abundance as estimated from the three technologies: Illumina, Nanopore, PacBio, for a single male individual (HG002). These differences depend on the technology used, thus revealing underlying biases. For example, estimates of AATGG were higher for Illumina, whereas some other repeats were predominantly captured by Nanopore or PacBio technology [183]. Repeats number 1–3, 7–9, and 17–20 were reprinted from the Supplementary Note 4 in [183]. Figure created with BioRender.com.