Interchromosomal segmental duplications of the pericentromeric region on the human Y chromosome

Abstract

Basic medical research critically depends on the finished human genome sequence. Two types of gaps are known to exist in the human genome: those associated with heterochromatic sequences and those embedded within euchromatin. We identified and analyzed a euchromatic island within the pericentromeric repeats of the human Y chromosome. This 450-kb island, although not recalcitrant to subcloning and present in 100 tested males from different ethnic origins, was not detected and is not contained within the published Y chromosomal sequence. The entire 450-kb interval is almost completely duplicated and consists predominantly of interchromosomal rather than intrachromosomal duplication events that are usually prevalent on the Y chromosome. We defined the modular structure of this interval and detected a total of 128 underlying pairwise alignments (Ն90% and Ն1 kb in length) to various autosomal pericentromeric and ancestral pericentromeric regions. We also analyzed the putative gene content of this region by a combination of in silico gene prediction and paralogy analysis. We can show that even in this exceptionally duplicated region of the Y chromosome, eight putative genes with open reading frames reside, including fusion transcripts formed by the splicing of exons from two different duplication modules as well as members of the homeobox gene family DUX.

Human centromere genomics: now it's personal

“…Although centromeric regions are commonly associated with compact, gene-poor heterochromatin, segmental duplications have been credited with "euchromatic colonization," introducing transcriptionally active landscapes capable of genetic innovation in the vicinity of centromeres (She et al 2004). In the human genome, characterized non-satellite euchromatic-like islands exist within the satellite-rich regions on chromosome 21p and in the pericentromeric region of chromosome Yq11 and, similarly, may represent a new dataset of previously uncharacterized segmental duplications within the inter-array "transitions" missing from our genomic model (Kirsch et al 2005;Lyle et al 2007). One may also speculate that even novel, single-copy sequences could occupy these regions through centromeric repositioning, establishing centromere identity within a region of the genome that, over time, is enclosed by satellite expansion (Montefalcone et al 1999).…”

Evolutionary dynamics of segmental duplications from human Y-chromosomal euchromatin/heterochromatin transition regions

“…. Recently, we characterized an additional euchromatic sequence from the Yq11.1/Yq11.21 euchromatin/heterochromatin transition region that is almost completely composed of interchromosomal segmental duplications (Kirsch et al 2005). Thorough inspection of the other three euchromatin/heterochromatin transition regions (Yp11.2/Yp11.1, Yq11.23/Yq12, Yq12/PAR2) revealed the existence of similarly complex structured sequences.…”

“…4; Supplemental Tables 4, 5; Kirsch et al 2005). Only three homologies to chromosomes 1, 11, and 14 could not be located in the chimpanzee genome under low stringency conditions.…”

“…The human orthologous regions for the latter two species are indicated in parentheses. Hybridization results for genomic clones from the Yq11.1/Yq11.21 region on human metaphase spreads were previously published in Kirsch et al (2005).…”

“…Recently, we have cloned a previously unknown euchromatic island within the pericentromeric satellite 3 sequences of the euchromatin/heterochromatin transition region in Yq11.1/Yq11.21 (Kirsch et al 2005). Whole-genome comparison of the assembled sequence revealed that it consisted exclusively of SDs.…”