An Optimized Set of Human Telomere Clones for Studying Telomere Integrity and Architecture

sequently, this resource has been optimized and completed: the size of the genomic clones has been expanded to a target size of 100--200 kb, which is optimal for use in genome-scanning methodologies, and additional probes for the remaining seven telomeres have been identified. For each clone we give an associated mapped sequence-tagged site and provide distances from the telomere estimated using a combination of fiberFISH, interphase FISH, sequence analysis, and radiation-hybrid mapping. This updated set of telomeric clones is an invaluable resource for clinical diagnosis and represents an important contribution to genetic and physical mapping efforts aimed at telomeric regions. Introduction The telomeric regions of human chromosomes are enriched for CpG islands and genes and are believed to have the highest gene density in the entire genome (Saccone et al. 1992). Characterization of telomeric regions is important for our understanding of the relationship between chr

A complete set of human telomeric probes and their clinical application

Human chromosomes terminate with specialized telomeric structures including the simple tandem repeat (TTAGGG)n and additional complex subtelomeric repeats. Unique sequence DNA for each telomere is located 100-300 kilobases (kb) from the end of most chromosomes. A high concentration of genes and a number of candidate genes for recognizable syndromes are known to be present in telomeric regions. The human telomeric regions represent a major diagnostic challenge in clinical cytogenetics, because most of the terminal bands are G negative, and cryptic deletions and translocations in the telomeric regions are therefore difficult to detect by conventional cytogenetic methods. In fact, several submicroscopic chromosomal abnormalities in patients with undiagnosed mental retardation or multiple congenital anomalies have been identified by other molecular methods such as DNA polymorphism analysis. To improve the sensitivity for deletion detection and to determine whether such cryptic rearrangements represent a significant source of human pathology that has not been previously appreciated, it would be valuable to have specific FISH probes for all human telomeres. We report here the isolation and characterization of a complete set of specific FISH probes representing each human telomere. As most of these clones are at a known distance of within 100-300 kb from the end of the chromosome arm, this provides a 10-fold improvement in deletion detection sensitivity compared with high-resolution cytogenetics (2-3 Mb resolution). While testing these probes, we serendipitously identified a family with multiple members carrying a cryptic 1q;11p rearrangement in the balanced or unbalanced state