A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration.
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 nu...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
1996
|
_version_ | 1797090110739578880 |
---|---|
author | Ning, Y Roschke, A Smith, A Macha, M Precht, K Riethman, H Ledbetter, D Flint, J Horsley, S Regan, R Kearney, L Knight, S Kvaloy, K Brown, W |
author_facet | Ning, Y Roschke, A Smith, A Macha, M Precht, K Riethman, H Ledbetter, D Flint, J Horsley, S Regan, R Kearney, L Knight, S Kvaloy, K Brown, W |
author_sort | Ning, Y |
collection | OXFORD |
description | 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. |
first_indexed | 2024-03-07T03:13:48Z |
format | Journal article |
id | oxford-uuid:b51a1acc-7e18-46cf-8334-4e2e361ae8d9 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T03:13:48Z |
publishDate | 1996 |
record_format | dspace |
spelling | oxford-uuid:b51a1acc-7e18-46cf-8334-4e2e361ae8d92022-03-27T04:30:54ZA complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b51a1acc-7e18-46cf-8334-4e2e361ae8d9EnglishSymplectic Elements at Oxford1996Ning, YRoschke, ASmith, AMacha, MPrecht, KRiethman, HLedbetter, DFlint, JHorsley, SRegan, RKearney, LKnight, SKvaloy, KBrown, WHuman 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. |
spellingShingle | Ning, Y Roschke, A Smith, A Macha, M Precht, K Riethman, H Ledbetter, D Flint, J Horsley, S Regan, R Kearney, L Knight, S Kvaloy, K Brown, W A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration. |
title | A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration. |
title_full | A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration. |
title_fullStr | A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration. |
title_full_unstemmed | A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration. |
title_short | A complete set of human telomeric probes and their clinical application. National Institutes of Health and Institute of Molecular Medicine collaboration. |
title_sort | complete set of human telomeric probes and their clinical application national institutes of health and institute of molecular medicine collaboration |
work_keys_str_mv | AT ningy acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT roschkea acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT smitha acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT macham acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT prechtk acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT riethmanh acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT ledbetterd acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT flintj acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT horsleys acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT reganr acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT kearneyl acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT knights acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT kvaloyk acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT brownw acompletesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT ningy completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT roschkea completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT smitha completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT macham completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT prechtk completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT riethmanh completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT ledbetterd completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT flintj completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT horsleys completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT reganr completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT kearneyl completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT knights completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT kvaloyk completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration AT brownw completesetofhumantelomericprobesandtheirclinicalapplicationnationalinstitutesofhealthandinstituteofmolecularmedicinecollaboration |