The relationship between chromosome structure and function at a human telomeric region

Abstract

We have sequenced a contiguous 284,495-bp segment of DNA extending from the terminal (TTAGGG)n repeats of the short arm of chromosome 16, providing a full description of the transition from telomeric through subtelomeric DNA to sequences that are unique to the chromosome. To complement and extend analysis of the primary sequence, we have characterized mRNA transcripts, patterns of DNA methylation and DNase I sensitivity. Together with previous data these studies describe in detail the structural and functional organization of a human telomeric region.

The Molecular Basis of -Thalassemia

“…This series of up-regulatory events taking place in erythroid cells is only a part of the complete story of a-globin regulation. Although the a-globin genes are expressed in a strictly tissuespecific manner, they are contained in a large chromosomal region, which is broadly transcriptionally active and bears the hallmarks of constitutively active chromatin (Flint et al 1997;Daniels et al 2001). Therefore, it was predicted that within such a region, mechanisms should exist to maintain the a-globin genes in a silent state in nonerythroid cells.…”

“…In addition to SNPs forming ancestral haplotypes (Higgs et al 1986), it had been shown that extensive polymorphic variations caused by genomic rearrangements were found in hematologically normal individuals. These variants are summarized in detail by Higgs (2009a) but the most notable small-scale variations in the a cluster occur in the many Grich VNTRs in this region (Flint et al 1997) together with the small-and large-scale variations commonly observed in the subtelomeric region of chromosome 16 (Wilkie et al 1991). Studies of the different arrangements of these polymorphisms and VNTRs in various population samples have made it possible to define a series of a-globin gene haplotypes that have been of considerable value both in the analysis of evolutionary aspects of the gene clusters and in defining the origins of many of the athalassemia mutations (Higgs et al 1986;Higgs 2009b).…”

Long Human–Mouse Sequence Alignments Reveal Novel Regulatory Elements: A Reason to Sequence the Mouse Genome

“…For instance, comparison of a long genomic DNA sequence with the expressed sequence tag (EST) databases is a very effective method for identifying many of the exons. A recent comparison of programs for predicting gene structures revealed that inclusion of protein sequence similarity searches improved performance (Burset and Guigó 1996), and the most efficient approach to identifying genes in a 284-kb sequence from the end of the short arm of human chromosome 16 was by comparison with the EST databases (Flint et al 1997). However, it is rare for the EST entries to encompass the complement to an entire mRNA, and hence all exon assignments usually cannot be obtained from the ESTs.…”

JTB: A novel membrane protein gene at 1q21 rearranged in a jumping translocation

“…Signi®cantly, it was found that variant telomeric repeats, such at TTGGGG, which have onebase substitutions in the canonical telomeric repeat TTAGGG, were dominant at the fusion points. These variant telomeric repeats are known to be present at the most centromeric (proximal) regions of the telomeres (Flint et al, 1997). Furthermore, it has been reported that telomeric repeats consisting solely of variant repeats might not perform some telomere functions in vivo (Hanish et al, 1994).…”