VARIATION IN THE FORKHEAD BOX CLASS O3 (FOXO3) GENE AND ITS ASSOCIATION WITH LIFESPAN TRAITS IN BARKI EWES

Authors

  • A. H. M. IBRAHIM Department of Animal Breeding, Desert Research Center, 1 Mathaf AlMatariya St., Cairo, Egypt
  • S. M. ALSHEIKH Department of Animal Breeding, Desert Research Center, 1 Mathaf AlMatariya St., Cairo, Egypt

Abstract

In this study the polymorphisms in exon 2 of ovine Forkhead Box Class O3 (FOXO3) gene were detected in 96 Barki ewes by the polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis. The association of FOXO3 gene polymorphisms with lifespan traits was tested using general linear mixed effect models. Three alleles (A, B and C) were detected with frequencies of 0.57, 0.28 and 0.15, respectively. Also five genotypes (AA, AB, AC, BB and CC) were identified with frequencies of 0.26, 0.44, 0.18, 0.06 and 0.06, respectively. Genotypes of the FOXO3 gene were shown to be associated with age, twining rate, total number of lambs born per ewe (TNLB) and total weight of lambs born per ewe (TWLB). The presence of allele C was associated with longer age and increased TNLB, whereas the presence of allele B was associated with shorter age, increased twining rate and decreased rearing ability and total number of lams weaned per ewe (TNLW). The effect of the number of allele copies present was tested and it was found that the presence of two copies of allele C was associated with longer age and increased TNLB and the presence of two copies of allele B was associated with shorter age, increased twining rate and decreased rearing ability and TNLW. These results suggest that variation in ovine FOXO3 gene is associated with lifespan traits of Barki ewes.

References

Anselmi, C. V., A. Malovini, R. Roncarati, V. Novelli, F. Villa, G. Condorelli, R. Bellazzi and A. A. Puca (2009). Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Research, 12: 95-104.

Bradford, G. E. (1985). Selection for litter size. In: R. B. Land and D. W. Robinson (Ed). Genetics of Reproduction in Sheep. Butterworths, London, p. 3-18.

Byun, S. O. K., H. Zhou and J. G. H. Hickford (2011). Characterization of Genetic Variation in the Forkhead Box Class O3 Gene (FOXO3) in Sheep. DNA and Cell Biology, 30: 449-452.

Byun, S. O., R. H. Forrest, H. Zhou, C. M. Frampton and J. G. H. Hickford (2013). Ovine forkhead box class O 3 (FOXO3) gene variation and its association with lifespan. Molecular Biology Reports, 405: 3829-3834.

Castrillon, D. H., L. Miao, R. Kollipara, J. W. Horner and R. A. DePinho (2003). Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science, 301: 215-218.

Chung, Y. M., S. Park, W. Tsai, S. Wang, M. Ikeda, J. S. Berek, D. J. Chen and M. Hu (2012). FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage. Nature Communications 3, Article number: 1000.

Flachsbart, F., A. Caliebe, R. Kleindorp, H. Blanché, H. von Eller-Eberstein, S. Nikolaus, S. Schreiber and A. Nebel (2009). Association of FOXO3A variation with human longevity confirmed in German centenarians. The Proceeding of the National Academy of Sciences of the United States of America, 1068: 2700-2705.

Gravina, S., F. Lescai and I. B. Roninson (2009). Identification of single nucleotide polymorphisms in the p21 (CDKN1A) gene and correlations with longevity in the Italian population. Aging, 1: 470-480.

He, Q., B. J. Morris, J. S. Grove, H. Petrovitch, W. Ross, K. H. Masaki, B. Rodriguez, R. Chen, D. A. Donlon and B. J. Willcox (2014). Shorter Men Live Longer: Association of Height with Longevity and FOXO3 Genotype in American Men of Japanese Ancestry. PLoS ONE 9: e94385. doi:10.1371/ journal.pone.0094385.

Hosaka, T., W. H. Biggs, D. Tieu, A. D. Boyer, N. M. Varki, W. K. Cavenee and K. C. Arden (2004). Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. The Proceeding of the National Academy of Sciences of the United States of America, 101: 2975-2980.

Hudson, M. B., J. A. Rahnert, B. Zheng, M. E. Woodworth-Hobbs, H. A. Franch and S. R. Price (2014). miR-182 attenuates atrophyrelated gene expression by targeting FoxO3 in skeletal muscle. American Journal of Physiology-Cell Physiology, 307: C314-C319. John, G. B., T. D. Gallardo, L. J. Shirley, and D. H. Castrillon (2008). Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth. Developmental Biology, 321: 197-204.

Kirkwood, T. B. L. and S. N. Austad (2000). Why do we age? Nature, 408: 233-238.

Kops, G. J. P. L., T. B. Dansen, P. E. Polderman, I. Saarloos, K. W. A. Wirtz, P. J. Coffer and B. M. T. Burgering (2002). Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature, 419: 316-321.

Ktbl (2009). Fleischschafhaltung- Produktionsverfahren planen und kalkulieren. (2009). Auflage, Kuratorium für Technik und Bauwesen in der Landwirtschaft e.V. (KTBL), Darmstadt.

Lee, J. C., M. Espéli, C. A. Anderson, M. A. Linterman, J. M. Pocock et al. (2013). Human snp links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway. Cell, 155: 57-69.

Li, Y., W. J. Wang, H. Cao, J. Lu, C. Wu, F. Y. Hu, J. Guo, L. Zhao, F. Yang, Y. X. Zhang et al. (2009). Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Human Molecular Genetics, 18: 4897-4904.

Litvak, V., A. V. Ratushny, A. E. Lampano, F. Schmitz, A. C. Huang, A. Raman, A. G. Rust, A. Bergthaler, J. D. Aitchison and A. Aderem (2012). A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses. Nature, 490: 421-425.

Mammucari, C., G. Milan, V. Romanello, E. Masiero, R. Rudolf, P. Del Piccolo, S. J. Burden, R. Di Lisi et al. (2007). FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metabolism, 6: 458-471.

Marinkovic, D., X. Zhang, S. Yalcin, J. P. Luciano, C. Brugnara, T. Huber and S. Ghaffar (2007). Foxo3 is required for the regulation of oxidative stress in erythropoiesis. The Journal of Clinical Investigation, 117: 2133-2144.

Mockett, R. J., R. S. Sohal and W. C. Orr (1999). Overexpression of glutathione reductase extends survival in transgenic Drosophila melanogaster under hyperoxia but not normoxia. The Journal of the Federation of American Societies for Experimental Biology, 13: 1733-1742.

Moniruzzaman, M, J. Lee, M. Zengyo and T. Miyano (2010). Knockdown of FOXO3 induces primordial oocyte activation in pigs. Reproduction, 139: 337-348.

Pawlikowska, L., D. Hu, S. Huntsman, A. Sung, C. Chu, J. Chen, A. H. Joyner et al. (2009). Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell, 8: 460-472.

Pelosi, E., S. Omari, M. Michel, J. Ding, T. Amano, A. Forabosco, D. Schlessinger and C. Ottolenghi (2013). Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice. Nature Communications, 4: 1843.

Renault, V. M., P. U. Thekkat, K. L. Hoang, J. L. White, C. A. Brady, D. Kenzelmann-Broz, O. S Venturelli., T. M. Johnson, P. R. Oskoui, Z. Xuan, E. E. Santo, M. Q. Zhang, H. Vogel, L. D. Attardi and A. Brunet (2011). The prolongevity gene FoxO3 is a direct target of the p53 tumor suppressor. Oncogene, Macmillan Publishers Limited, p. 1-15.

Salcher, S., J. Hagenbuchner, K. Geiger, M. A. Seiter, J. Rainer, R. Kofler, M. Hermann, U. Kiechl-Kohlendorfer, M. J. Ausserlechner and P. Obexer (2014). C10ORF10/DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma. Molecular Cancer, 13: 224.

Sanguinetti, C. J., E. Dias Neto and A. J. G. Simpson (1994). Rapid silver staining and recovery of PCR products separated on polyacrylamide gels. Biotechniques, 17: 915-919.

Savkovic, S. D. (2013). Decreased FOXO3 within advanced human colon cancer: implications of tumour suppressor function. British Journal of Cancer, 109: 297-298.

Schriner, S. E., N. J. Linford, G. M. Martin, P. Treuting, C. S. Ogburn, M. Emond, P. E. Coskun, W. N. Wolf, H. Van Remmen and D. C. Wallace (2005). Extension of Murine Life Span by Overexpression of Catalase Targeted to Mitochondria. Science, 308: 1909-1911.

Seoane, J., H. V. Le, L. Shen, S. A. Anderson and J. Massague (2004). Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation. Cell, 117: 211-223.

Soerensen, M., S. Dato, K. Christensen, M. McGue, T. Stevnsner, V. A. Bohr and L. Christiansen (2010). Replication of an association of variation in the FOXO3A gene with human longevity using both casecontrol and longitudinal data. Aging Cell, 9: 1010-1017.

Sun, J., D. Folk, T. J. Bradley and J. Tower (2002). Induced overexpression of mitochondrial Mnsuperoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics, 16: 661-672.

Tran, H., A. Brunet, J. M. Grenier, S. R. Datta, A. J. Fornace, P. S. DiStefano and M. E. Greenberg (2002). DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science, 296: 530-534.

Vukasinovic, N. (1999). Application of Survival Analysis in Breeding for

Longevity. 21st Interbull Meeting, Jouyen-Josas, France. Interbull Bulletin, 21: 3-10.

Wang, B., Y. Mu, F. Ni, S. Zhou, J. Wang, Y. Cao and X. Ma (2010). Analysis of FOXO3 mutation in 114 Chinese women with premature ovarian failure. Reproductive Biomedicine Online, 20: 499-503.

Willcox, B. J., T. A. Donlon, Q. He, R. Chen, G. S. Grove, K. Yano, K. H. Masaki, D. C. Willcox, B. Rodriguez and J. D. Curb (2008). FOXO3A genotype is strongly associated with human longevity. The Proceeding of the National Academy of Sciences of the United States of America, 105: 13987-13992.

Downloads

Published

2016-01-12

Issue

Section

Articles