ABSTRACT

FSHD Facioscapulohumeral Muscular Dystrophy: Clinical Medicine and Molecular Cell Biology, edited by Meena Upadhyaya and David N.Cooper. © 2004 Garland/BIOS Scientific Publishers Limited, Abingdon.

8.1 Introduction

Telomeres define the most distal genetic and physical boundaries of chromosomes and consist of essential structures that ensure the stability of the genome. The human telomere itself consists of a distinct tandemly repeated structure of (TTAGGG)n. Between this array and the unique chromosome-specific sequence, there is a complex and variable region of the chromosome: the subtelomere. This region varies between chromosomes, although there is extensive sharing of sequence domains suggesting a complex pattern of duplications between subtelomeres of different chromosomes (Flint et al., 1997a, 1997b). Some of these duplication events are estimated to have occurred quite recently, between 5 and 25 million years ago (Martin et al., 2002). The complexity and dynamic nature of these genomic regions is reviewed by Mefford and Trask (2002). In this chapter, we provide an overview of what is known about the organization of the human chromosome 4q and 10q telomeres. The relationships between these two subtelomeres and the implications for the FSHD disease mechanism are highlighted.