Home LiteratureArticle Details
PMID: 16552446 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Telomere length as a quantitative trait: genome-wide survey and genetic mapping of telomere length-control genes in yeast.

PLoS genetics ·Vol. 2 ·No. 3 ·2006-03-00 ·Pages e35

Gatbonton T, Imbesi M, Nelson M, Akey JM, Ruderfer DM, Kruglyak L, Simon JA, Bedalov A

Abstract

Telomere length-variation in deletion strains of Saccharomyces cerevisiae was used to identify genes and pathways that regulate telomere length. We found 72 genes that when deleted confer short telomeres, and 80 genes that confer long telomeres relative to those of wild-type yeast. Among identified genes, 88 have not been previously implicated in telomere length control. Genes that regulate telomere length span a variety of functions that can be broadly separated into telomerase-dependent and telomerase-independent pathways. We also found 39 genes that have an important role in telomere maintenance or cell proliferation in the absence of telomerase, including genes that participate in deoxyribonucleotide biosynthesis, sister chromatid cohesion, and vacuolar protein sorting. Given the large number of loci identified, we investigated telomere lengths in 13 wild yeast strains and found substantial natural variation in telomere length among the isolates. Furthermore, we crossed a wild isolate to a laboratory strain and analyzed telomere length in 122 progeny. Genome-wide linkage analysis among these segregants revealed two loci that account for 30%-35% of telomere length-variation between the strains. These findings support a general model of telomere length-variation in outbred populations that results from polymorphisms at a large number of loci. Furthermore, our results laid the foundation for studying genetic determinants of telomere length-variation and their roles in human disease.

MeSH Terms
Chromosome Mapping/methods Chromosomes, Fungal Fungal Proteins/genetics Gene Deletion Genes, Fungal Genome, Fungal Polymorphism, Genetic Quantitative Trait Loci Saccharomyces cerevisiae/genetics Silent Information Regulator Proteins, Saccharomyces cerevisiae/genetics Sister Chromatid Exchange Telomere/ultrastructure
Chemicals
Fungal Proteins Silent Information Regulator Proteins, Saccharomyces cerevisiae
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Gatbonton Tonibelle
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Imbesi Maria
Nelson Melisa
Akey Joshua M
Ruderfer Douglas M
Kruglyak Leonid
Simon Julian A
Bedalov Antonio
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

References (44)
44 references, click to expand
  1. A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length.
    Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8658-63 PMID: 15161972
  2. The Paf1 complex has functions independent of actively transcribing RNA polymerase II.
    Mol Cell. 2004 May 21;14(4):447-56 PMID: 15149594
  3. Regulation of murine telomere length by Rtel: an essential gene encoding a helicase-like protein.
    Cell. 2004 Jun 25;117(7):873-86 PMID: 15210109
  4. In situ analyses of genome instability in breast cancer.
    Nat Genet. 2004 Sep;36(9):984-8 PMID: 15300252
  5. Does the reservoir for self-renewal stem from the ends?
    Oncogene. 2004 Sep 20;23(43):7283-9 PMID: 15378088
  6. Origin of concatemeric T7 DNA.
    Nat New Biol. 1972 Oct 18;239(94):197-201 PMID: 4507727
  7. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon.
    J Theor Biol. 1973 Sep 14;41(1):181-90 PMID: 4754905
  8. Genetic control of chromosome length in yeast.
    Proc Natl Acad Sci U S A. 1985 Jan;82(2):506-10 PMID: 2982162
  9. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.
    Cell. 1985 Dec;43(2 Pt 1):405-13 PMID: 3907856
  10. A mutant with a defect in telomere elongation leads to senescence in yeast.
    Cell. 1989 May 19;57(4):633-43 PMID: 2655926
  11. An alternative pathway for yeast telomere maintenance rescues est1- senescence.
    Cell. 1993 Apr 23;73(2):347-60 PMID: 8477448
  12. The chromosome end in yeast: its mosaic nature and influence on recombinational dynamics.
    Genetics. 1994 Mar;136(3):789-802 PMID: 8005434
  13. TLC1: template RNA component of Saccharomyces cerevisiae telomerase.
    Science. 1994 Oct 21;266(5184):404-9 PMID: 7545955
  14. Genetic modulation of telomeric terminal restriction-fragment length: relevance for clonal aging and late-life disease.
    Am J Hum Genet. 1994 Nov;55(5):866-9 PMID: 7977347
  15. Genetic determination of telomere size in humans: a twin study of three age groups.
    Am J Hum Genet. 1994 Nov;55(5):876-82 PMID: 7977349
  16. Isolation and characterization of two Saccharomyces cerevisiae genes that encode proteins that bind to (TG1-3)n single strand telomeric DNA in vitro.
    Nucleic Acids Res. 1994 Nov 25;22(23):4906-13 PMID: 7800479
  17. Replicative senescence and cell death.
    Science. 1995 Jan 6;267(5194):17 PMID: 7848496
  18. Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae.
    Cell. 2001 Feb 9;104(3):397-408 PMID: 11239397
  19. Telomeric chromatin: replicating and wrapping up chromosome ends.
    Curr Opin Genet Dev. 2001 Apr;11(2):189-98 PMID: 11250143
  20. Cellular senescence, cancer and aging: the telomere connection.
    Exp Gerontol. 2001 Nov;36(10):1619-37 PMID: 11672984
  21. Systematic genetic analysis with ordered arrays of yeast deletion mutants.
    Science. 2001 Dec 14;294(5550):2364-8 PMID: 11743205
  22. Genetic dissection of transcriptional regulation in budding yeast.
    Science. 2002 Apr 26;296(5568):752-5 PMID: 11923494
  23. Mechanisms of chromosome-end protection.
    Curr Opin Cell Biol. 2002 Jun;14(3):351-6 PMID: 12067658
  24. Functional profiling of the Saccharomyces cerevisiae genome.
    Nature. 2002 Jul 25;418(6896):387-91 PMID: 12140549
  25. Chromosomal instability in ulcerative colitis is related to telomere shortening.
    Nat Genet. 2002 Oct;32(2):280-4 PMID: 12355086
  26. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter.
    Mol Cell. 2003 Jan;11(1):267-74 PMID: 12535539
  27. Association between telomere length in blood and mortality in people aged 60 years or older.
    Lancet. 2003 Feb 1;361(9355):393-5 PMID: 12573379
  28. mRNAs encoding telomerase components and regulators are controlled by UPF genes in Saccharomyces cerevisiae.
    Eukaryot Cell. 2003 Feb;2(1):134-42 PMID: 12582130
  29. Rfm1, a novel tethering factor required to recruit the Hst1 histone deacetylase for repression of middle sporulation genes.
    Mol Cell Biol. 2003 Mar;23(6):2009-16 PMID: 12612074
  30. Genome renewal: a new phenomenon revealed from a genetic study of 43 strains of Saccharomyces cerevisiae derived from natural fermentation of grape musts.
    Yeast. 1994 Dec;10(12):1543-52 PMID: 7725789
  31. Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes.
    Genetics. 1996 Dec;144(4):1399-412 PMID: 8978029
  32. Structure, function, and replication of Saccharomyces cerevisiae telomeres.
    Annu Rev Genet. 1996;30:141-72 PMID: 8982452
  33. Yeast Ku as a regulator of chromosomal DNA end structure.
    Science. 1998 May 1;280(5364):741-4 PMID: 9563951
  34. Telomere length regulation in mice is linked to a novel chromosome locus.
    Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8648-53 PMID: 9671732
  35. Telomere length regulation and telomeric chromatin require the nonsense-mediated mRNA decay pathway.
    Mol Cell Biol. 1998 Oct;18(10):6121-30 PMID: 9742129
  36. RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase.
    Genetics. 1999 May;152(1):143-52 PMID: 10224249
  37. Mapping of a major locus that determines telomere length in humans.
    Am J Hum Genet. 2005 Jan;76(1):147-51 PMID: 15520935
  38. The yeast VPS genes affect telomere length regulation.
    Curr Genet. 2005 Jan;47(1):18-28 PMID: 15551135
  39. Limited TTP supply affects telomere length regulation in a telomerase-independent fashion.
    Nucleic Acids Res. 2005;33(2):704-13 PMID: 15681620
  40. The landscape of genetic complexity across 5,700 gene expression traits in yeast.
    Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1572-7 PMID: 15659551
  41. Regulation of telomerase by telomeric proteins.
    Annu Rev Biochem. 2004;73:177-208 PMID: 15189140
  42. R/qtl: QTL mapping in experimental crosses.
    Bioinformatics. 2003 May 1;19(7):889-90 PMID: 12724300
  43. Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors.
    Nat Genet. 2003 Sep;35(1):57-64 PMID: 12897782
  44. Beginning to understand the end of the chromosome.
    Cell. 2004 Jan 23;116(2):273-9 PMID: 14744437
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.0020035
Published
2006-03-00
Epub
2006-00-17
Pages
e35
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC1401499
Subset
IM
Grants
NIMH NIH HHS · R37 MH059520 · United States
NCI NIH HHS · P20 CA103728 · United States
NCI NIH HHS · CA 103728 · United States
NHLBI NIH HHS · HL04211 · United States
NIMH NIH HHS · R37 MH59520 · United States
NCI NIH HHS · CA 78746 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1371/journal.pgen.0020035 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2