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General Information
Flow-FISH measurements have been shown to be valuable as a screening test for inherited telomere maintenance deficiencies resulting from mutations in dyskerin, telomerase RNA (hTERC), telomerase reverse transcriptase (hTERT) and other genes.
Deficiencies in these genes are known to predispose to a variety of clinical disorders including forms of aplastic anemia, pulmonary fibrosis, liver cirrhosis and dyskeratosis congenita. Distinction between acquired and inherited factors contributing to these and other diseases is important for prognosis and therapeutic considerations.
To get a general idea whether telomere length has been affected, we offer the BASIC PROCEDURE. This procedure provides measurements of telomere length for total lymphocyte and granulocyte populations.
In more specialized situations, however, this procedure may not be informative enough. E.g. in most aplastic anemia patients, the granulocyte telomere lengths will be low and lymphocytes may be borderline. When testing patients with diseases related to mutations in telomere maintenance genes, the DETAILED PROCEDURE is more appropriate. With this procedure, telomere lengths are measured not only for total lymphocyte and granulocyte populations, but also for B-cells, T-cells and NK cells.
Download Related Peer-Reviewed Scientific Publications
Click here to download and print an up-to-date list of related peer-reviewed scientific publications, or peruse the publicly available online publications below.
Online Related Peer-Reviewed Scientific Publications
1. Baerlocher, G. M., Vulto, I., de Jong, G. & Lansdorp, P. M. Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nat Protoc 1, 2365-76 (2006).
2. Alter, B. P. et al. Very short telomere length by flow FISH identifies patients with Dyskeratosis Congenita. Blood (2007).
3. Armanios, M. Y. et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med 356, 1317-26 (2007).
4. Ly, H. et al. Functional characterization of telomerase RNA variants found in patients with hematologic disorders. Blood 105, 2332-9 (2005).
5. Ly, H. et al. Identification and functional characterization of 2 variant alleles of the telomerase RNA template gene (TERC) in a patient with dyskeratosis congenita. Blood 106, 1246-52 (2005).
6. Yamaguchi, H. et al. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med 352, 1413-24 (2005).
7. Savage S.S.,Giri N, Baerlocher, G.M., Orr, N., Lansdorp P.M., and Alter, B.P. TINF2, a Component of the Shelterin Telomere Protection Complex, is Mutated in Dyskeratosis Congenita. Am. J. Hum. Gen. 82(2): 501-9 (2008).
8. Fogarty, P. F. et al. Late presentation of dyskeratosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase RNA. Lancet 362, 1628-30 (2003).
9. Baerlocher, G. M., Rice, K., Vulto, I. & Lansdorp, P. M. Longitudinal data on telomere length in leukocytes from newborn baboons support a marked drop in stem cell turnover around 1 year of age. Aging Cell 6, 121-3 (2007).
10. Rufer, N. et al. Accelerated telomere shortening in hematological lineages is limited to the first year following stem cell transplantation. Blood 97, 575-7 (2001).
11. Rufer, N. et al. Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J Exp Med 190, 157-67 (1999).
12. Parry, E.M. et al. Decreased dyskerin levels as a mechanism of telomere shortening in X-linked dyskeratosis congenita. J Med Genet. (2011).
Telomeres in the News
May 25, 2011, European Journal of Human Genetics: Clinical utility gene card found for Dyskeratosis Congenita
November 28, 2010, Nature Online: Telomerase reverses ageing process. Dramatic rejuvenation of prematurely aged mice hints at potential therapy.
December 10, 2009, The Nobel Prize in Physiology or Medicine 2009 has been awarded "for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase."
February 15, 2008, Blood, Vol. 111, No. 4, pp. 1759-1766:
ASH 50TH ANNIVERSARY REVIEW on Telomeres, stem cells, and hematology
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Longer telomeres: more fluorescence.
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