Effects of age on segregation of the X and Y chromosomes in cultured lymphocytes from Chinese men

a.
Laboratory of Molecular and Cell Genetics, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
b.
Department of Science of Biology, Bengbu Medical Collage, Bengbu 233000, China

More Information

Corresponding author: E-mail address: qshi@ustc.edu.cn (Qinghua Shi)

摘要

- /
- /
- /
- /
- /
Abstract: Chromosome malsegregation in binucleated lymphocytes is a useful endpoint to evaluate age effect on genetic stability. However, theinvestigations on chromosome malsegregation in binucleated lymphocytes from Chinese are scarce. In this study, peripheral blood lymphocytes were collected from 14 old (60–70 years) and 10 young (22–26 years) healthy Chinese men. To detect malsegregation of the sexchromosomes, multi-color fluorescence in situ hybridization (FISH) was performed on binucleated lymphocytes, cytokinesis-blocked bycytochalasin B at the first mitosis after phytohaemagglutinin stimulation. Compared with that in young men, a significant increase in frequencies of loss of chromosome X (9.2 ± 3.2‰vs. 1.1 ± 0.9‰, P < 0.001) and Y (2.5 ± 1.9‰ vs. 0.2 ± 0.3‰, P < 0.001) was found inold men. Similarly, nondisjunction of chromosome X (16.5 ± 3.4‰ vs. 3.5 ± 1.1‰, P < 0.001) and Y (7.2 ± 2.6‰ vs. 2.4 ± 1.3‰, P < 0.001) occurred more frequently in old men than in young men. Regardless of donor's age, nondisjunction is more prevalent than loss forboth chromosome X and Y. The frequencies of observed simultaneous malsegregation were relatively higher than the expected, suggesting an association between malsegregation. These results indicated that in Chinese men, malsegregation of the sex chromosomes increases with age in an associated fashion, and nondisjunction accounts for the majority of spontaneous chromosome malsegregation.
- chromosome loss /
- nondisjunction /
- chromosome X /
- chromosome Y /
- lymphocyte /
- Chinese men

HTML全文

参考文献(39)

[1]	Baker, D.J., Jeganathan, K.B., Cameron, J.D. et al. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice Nat. Genet., 36 (2004),pp. 744-749
[2]	Bakou, K., Stephanou, G., Andrianopoulos, C. et al. Spontaneous and spindle poison-induced micronuclei and chromosome non-disjunction in cytokinesis-blocked lymphocytes from two age groups of women Mutagenesis, 17 (2002),pp. 233-239
[3]	Boffetta, P., van der Hel, O., Norppa, H. et al. Chromosomal aberrations and cancer risk: Results of a cohort study from Central Europe Am. J. Epidemiol., 165 (2007),pp. 36-43
[4]	Bonassi, S., Znaor, A., Ceppi, M. et al. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans Carcinogenesis, 28 (2007),pp. 625-631
[5]	Carere, A., Antoccia, A., Cimini, D. et al. Analysis of chromosome loss and non-disjunction in cytokinesis-blocked lymphocytes of 24 male subjects Mutagenesis, 14 (1999),pp. 491-496
[6]	Catalan, J., Autio, K., Kuosma, E. et al. Age-dependent inclusion of sex chromosomes in lymphocyte micronuclei of man Am. J. Hum. Genet., 63 (1998),pp. 1464-1472
[7]	Catalan, J., Surralles, J., Falck, G.C. et al. Segregation of sex chromosomes in human lymphocytes Mutagenesis, 15 (2000),pp. 251-255
[8]	Cimini, D., Degrassi, F. Aneuploidy: A matter of bad connections Trends Cell Biol., 15 (2005),pp. 442-451
[9]	Cleveland, D.W., Mao, Y., Sullivan, K.F. Centromeres and kinetochores: From epigenetics to mitotic checkpoint signaling Cell, 112 (2003),pp. 407-421
[10]	Fenech, M., Morley, A.A. Kinetochore detection in micronuclei: An alternative method for measuring chromosome loss Mutagenesis, 4 (1989),pp. 98-104
[11]	Fenech, M. Cytokinesis-block micronucleus cytome assay Nat. Protoc., 2 (2007),pp. 1084-1104
[12]	Fenech, M. Genome health nutrigenomics and nutrigenetics–diagnosis and nutritional treatment of genome damage on an individual basis Food Chem. Toxicol., 46 (2008),pp. 1365-1370
[13]	Griffin, D.K., Abruzzo, M.A., Millie, E.A. et al. Non-disjunction in human sperm: Evidence for an effect of increasing paternal age Hum. Mol. Genet., 4 (1995),pp. 2227-2232
[14]	Guttenbach, M., Koschorz, B., Bernthaler, U. et al. Am. J. Hum. Genet., 57 (1995),pp. 1143-1150
[15]	Hando, J.C., Nath, J., Tucker, J.D. Sex chromosomes, micronuclei and aging in women Chromosoma, 103 (1994),pp. 186-192
[16]	Hodges, C.A., Revenkova, E., Jessberger, R. et al. SMC1beta-deficient female mice provide evidence that cohesins are a missing link in age-related nondisjunction Nat. Genet., 37 (2005),pp. 1351-1355
[17]	Jacobs, P.A., Court Brown, W.M., Doll, R. Distribution of human chromosome counts in relation to age Nature, 191 (1961),pp. 1178-1180
[18]	Jin, C., Jin, Y., Wennerberg, J. et al. Clonal chromosome aberrations accumulate with age in upper aerodigestive tract mucosa Mutat. Res., 374 (1997),pp. 63-72
[19]	Kirsch-Volders, M., Tallon, I., Tanzarella, C. et al. Mutagenesis, 11 (1996),pp. 307-313
[20]	Lubs, H.A., Kinberling, W.J., Hecht, F. et al. Racial differences in the frequency of Q and C chromosomal heteromorphisms Nature, 268 (1977),pp. 631-633
[21]	McMurray, M.A., Gottschling, D.E. Aging and genetic instability in yeast Curr. Opin. Microbiol., 7 (2004),pp. 673-679
[22]	Mukherjee, A.B., Thomas, S., Schmitt, E. Mech. Ageing Dev., 80 (1995),pp. 11-23
[23]	Murnane, J.P. Telomeres and chromosome instability DNA Repair (Amst), 5 (2006),pp. 1082-1092
[24]	Nath, J., Tucker, J.D., Hando, J.C. Y chromosome aneuploidy, micronuclei, kinetochores and aging in men Chromosoma, 103 (1995),pp. 725-731
[25]	Neurath, P., DeRemer, K., Bell, B. et al. Chromosome loss compared with chromosome size, age and sex of subjects Nature, 225 (1970),pp. 281-282
[26]	Pan, H., Ma, P., Zhu, W. et al. Age-associated increase in aneuploidy and changes in gene expression in mouse eggs Dev. Biol., 316 (2008),pp. 397-407
[27]	Richard, F., Muleris, M., Dutrillaux, B. The frequency of micronuclei with X chromosome increases with age in human females Mutat. Res., 316 (1994),pp. 1-7
[28]	Rieder, C.L., Maiato, H. Stuck in division or passing through: What happens when cells cannot satisfy the spindle assembly checkpoint Dev. Cell., 7 (2004),pp. 637-651
[29]	Shi, Q., Chen, J., Adler, I. et al. Increased nondisjunction of chromosome 21 with age in human peripheral lymphocytes Mutat. Res., 452 (2000),pp. 27-36
[30]	Shi, Q., Martin, R.H. Am. J. Med. Genet., 93 (2000),pp. 40-46
[31]	Stone, J.F., Sandberg, A.A. Sex chromosome aneuploidy and aging Mutat. Res., 338 (1995),pp. 107-113
[32]	Vogt, E., Kirsch-Volders, M., Parry, J. et al. Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error Mutat. Res., 651 (2008),pp. 14-29
[33]	Wang, L.E., Xiong, P., Zhao, H. et al. Chromosome instability and risk of squamous cell carcinomas of head and neck Cancer Res., 68 (2008),pp. 4479-4485
[34]	Wojda, A., Zietkiewicz, E., Mossakowska, M. et al. Correlation between the level of cytogenetic aberrations in cultured human lymphocytes and the age and gender of donors J. Gerontol. A Biol. Sci. Med. Sci., 61 (2006),pp. 763-772
[35]	Wojda, A., Zietkiewicz, E., Witt, M. Effects of age and gender on micronucleus and chromosome nondisjunction frequencies in centenarians and younger subjects Mutagenesis, 22 (2007),pp. 195-200
[36]	Wyandt, H.E., Tonk, V.S.
[37]	Zijno, A., Marcon, F., Leopardi, P. et al. Mutagenesis, 9 (1994),pp. 225-232
[38]	Zijno, A., Leopardi, P., Marcon, F. et al. Sex chromosome loss and non-disjunction in women: Analysis of chromosome segregation in binucleated lymphocytes Chromosoma, 104 (1996),pp. 461-467
[39]	Zijno, A., Leopardi, P., Marcon, F. et al. Mutat. Res., 372 (1996),pp. 211-219