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Front Genet. 2011 Sep 27;2:63. doi: 10.3389/fgene.2011.00063. eCollection 2011.

A narrow quantitative trait locus in C. elegans coordinately affects longevity, thermotolerance, and resistance to paraquat.

Frontiers in genetics

Anthony Vertino, Srinivas Ayyadevara, John J Thaden, Robert J Shmookler Reis

Affiliations

  1. Veterans Affairs Medical Center, Central Arkansas Veterans Health Care System Little Rock, and University of Arkansas for Medical Sciences, Little Rock, AR, USA.

PMID: 22303358 PMCID: PMC3268616 DOI: 10.3389/fgene.2011.00063

Abstract

By linkage mapping of quantitative trait loci, we previously identified at least 11 natural genetic variants that significantly modulate Caenorhabditis elegans life-span (LS), many of which would have eluded discovery by knock-down or mutation screens. A region on chromosome IV between markers stP13 and stP35 had striking effects on longevity in three inter-strain crosses (each P < 10(-9)). In order to define the limits of that interval, we have now constructed two independent lines by marker-based selection during 20 backcross generations, isolating the stP13-stP35 interval from strain Bergerac-BO in a CL2a background. These congenic lines differed significantly from CL2a in LS, assayed in two environments (each P < 0.001). We then screened for exchange of flanking markers to isolate recombinants that partition this region, because fine-mapping the boundaries for overlapping heteroallelic spans can greatly narrow the implicated interval. Recombinants carrying the CL2a allele at stP35 were consistently long-lived compared to those retaining the Bergerac-BO allele (P < 0.001), and more resistant to temperature elevation and paraquat (each ∼1.7-fold, P < 0.0001), but gained little protection from ultraviolet or peroxide stresses. Two rounds of recombinant screening, followed by fine-mapping of break-points and survival testing, narrowed the interval to 0.18 Mb (13.35-13.53 Mb) containing 26 putative genes and six small-nuclear RNAs - a manageable number of targets for functional assessment.

Keywords: life-span; linkage mapping; longevity; oxidative stress; recombinant-congenic lines; thermotolerance; ultraviolet irradiation, C. elegans

References

  1. Exp Gerontol. 2006 Oct;41(10):1046-54 - PubMed
  2. Curr Opin Biotechnol. 2007 Aug;18(4):355-9 - PubMed
  3. J Gerontol A Biol Sci Med Sci. 1999 Apr;54(4):B137-42 - PubMed
  4. Science. 2000 Oct 6;290(5489):147-50 - PubMed
  5. J Clin Endocrinol Metab. 2003 Jul;88(7):3299-304 - PubMed
  6. Genetica. 2002 Mar;114(2):147-56 - PubMed
  7. Mech Ageing Dev. 1983 Jul-Aug;22(3-4):279-86 - PubMed
  8. Phys Biol. 2011 Aug;8(4):046007 - PubMed
  9. PLoS Genet. 2007 Apr 6;3(4):e56 - PubMed
  10. Philos Trans R Soc Lond B Biol Sci. 1991 Apr 29;332(1262):15-24 - PubMed
  11. Nature. 2009 Jul 16;460(7253):396-9 - PubMed
  12. Genetics. 1992 Jul;131(3):609-24 - PubMed
  13. Genetics. 2000 Jan;154(1):213-27 - PubMed
  14. Nature. 1999 Dec 16;402(6763):804-9 - PubMed
  15. Evolution. 2002 Oct;56(10):1982-91 - PubMed
  16. Dev Genet. 1996;18(2):131-43 - PubMed
  17. Mech Ageing Dev. 2002 Apr;123(7):765-71 - PubMed
  18. Curr Biol. 2007 Oct 9;17(19):1646-56 - PubMed
  19. Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E1064-71 - PubMed
  20. Anal Biochem. 2000 Aug 15;284(1):11-8 - PubMed
  21. Anal Biochem. 2000 Aug 15;284(1):19-28 - PubMed
  22. Science. 2007 Jul 20;317(5836):369-72 - PubMed
  23. Mech Ageing Dev. 2007 Jan;128(1):106-11 - PubMed
  24. Genetics. 1998 Feb;148(2):703-17 - PubMed
  25. Mech Ageing Dev. 2004 Mar;125(3):179-89 - PubMed
  26. Aging Cell. 2007 Feb;6(1):95-110 - PubMed
  27. Genome Biol Evol. 2011;3:320-31 - PubMed
  28. Science. 2000 Sep 22;289(5487):2126-8 - PubMed
  29. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13091-6 - PubMed
  30. J Clin Invest. 2006 Sep;116(9):2464-72 - PubMed
  31. PLoS Genet. 2009 Apr;5(4):e1000452 - PubMed
  32. PLoS Genet. 2005 Jul;1(1):119-28 - PubMed
  33. Genetics. 1995 Apr;139(4):1567-83 - PubMed
  34. Genetics. 2003 Feb;163(2):557-70 - PubMed
  35. Genome Biol. 2007;8(12):R262 - PubMed
  36. Nature. 1993 Dec 2;366(6454):461-4 - PubMed
  37. Biochim Biophys Acta. 2009 Oct;1790(10):1075-83 - PubMed
  38. J Exp Biol. 2007 May;210(Pt 9):1607-12 - PubMed
  39. Nature. 2000 Nov 9;408(6809):255-62 - PubMed
  40. Mech Ageing Dev. 2007 Mar;128(3):237-49 - PubMed
  41. Science. 2001 Apr 6;292(5514):107-10 - PubMed
  42. Aging Cell. 2009 Dec;8(6):706-25 - PubMed
  43. Mol Biol Cell. 2004 Feb;15(2):657-64 - PubMed
  44. J Mol Evol. 1995 Apr;40(4):372-81 - PubMed
  45. Genetics. 1995 Mar;139(3):1247-59 - PubMed
  46. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6603-7 - PubMed
  47. Science. 2002 Dec 20;298(5602):2398-401 - PubMed
  48. Genetics. 1996 Mar;142(3):801-17 - PubMed
  49. Genetics. 2001 Feb;157(2):655-66 - PubMed
  50. Sci Aging Knowledge Environ. 2004 Aug 04;2004(31):re5 - PubMed
  51. Genetics. 2000 Nov;156(3):1129-46 - PubMed
  52. Exp Aging Res. 2002 Oct-Dec;28(4):361-90 - PubMed
  53. Genetics. 1999 Nov;153(3):1233-43 - PubMed
  54. Aging Cell. 2004 Oct;3(5):297-307 - PubMed
  55. Mech Ageing Dev. 2005 Mar;126(3):381-7 - PubMed
  56. Genetics. 2006 Mar;172(3):1595-605 - PubMed
  57. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7540-4 - PubMed
  58. Exp Gerontol. 2008 Oct;43(10):882-91 - PubMed
  59. Cell. 2006 Jun 16;125(6):1165-77 - PubMed
  60. Cell Metab. 2010 Jun 9;11(6):453-65 - PubMed
  61. PLoS Genet. 2010 Jul 29;6(7):e1001037 - PubMed
  62. Mech Ageing Dev. 2005 Jun-Jul;126(6-7):642-7 - PubMed
  63. Nature. 2004 Aug 5;430(7000):686-9 - PubMed
  64. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18046-9 - PubMed
  65. Neurobiol Aging. 1999 Sep-Oct;20(5):503-12 - PubMed
  66. Ann N Y Acad Sci. 2000 Jun;908:324-6 - PubMed
  67. Genet Res. 2002 Dec;80(3):225-30 - PubMed
  68. Aging Cell. 2009 Apr;8(2):113-27 - PubMed
  69. Genetics. 1993 Dec;135(4):1003-10 - PubMed
  70. Dev Genet. 1996;18(2):144-53 - PubMed
  71. Genetics. 1996 Jul;143(3):1193-205 - PubMed
  72. Aging Cell. 2005 Oct;4(5):235-45 - PubMed
  73. Science. 1996 May 17;272(5264):1010-3 - PubMed
  74. Cell Metab. 2008 Aug;8(2):118-31 - PubMed
  75. Genetics. 2004 Jan;166(1):161-9 - PubMed
  76. BMC Dev Biol. 2006 Oct 04;6:45 - PubMed
  77. Aging (Albany NY). 2011 Feb;3(2):125-47 - PubMed
  78. Genome Biol. 2007;8(7):R132 - PubMed
  79. PLoS Genet. 2006 Nov 10;2(11):e183 - PubMed
  80. J Biol Chem. 2004 Oct 22;279(43):44533-43 - PubMed
  81. PLoS One. 2010 Jan 18;5(1):e8758 - PubMed
  82. PLoS Genet. 2010 May 13;6(5):e1000950 - PubMed
  83. Genome Res. 2000 Nov;10(11):1690-6 - PubMed
  84. Nature. 1998 Aug 13;394(6694):694-7 - PubMed
  85. Genetics. 2000 Aug;155(4):1773-88 - PubMed
  86. Neuron. 2009 Mar 12;61(5):692-9 - PubMed
  87. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9734-9 - PubMed
  88. Aging Cell. 2008 Jan;7(1):13-22 - PubMed
  89. Genetics. 1988 Jan;118(1):75-86 - PubMed

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