Content area
Full text
(ProQuest: ... denotes non-US-ASCII text omitted.)
1. Introduction
Down syndrome (DS), the most frequent live born aneuploidy in human, is predominantly caused by trisomy of chromosome 21 (Ch 21) and its aetiologic factors are under continuous scrutiny since its discovery by Lejeune et al. (1959). Several groups of workers have tried to explore the factors associated with non-disjunction (NDJ) of Ch 21 and have identified advanced maternal age (Hassold & Chiu, 1985; Allen et al., 2009) and altered pattern of recombination of maternal non-disjoined chromosomes (Warren et al., 1987; Sherman et al., 1991; Oliver et al., 2008) as two strong correlates that affect proper segregation of chromosomes at oogenesis, particularly at first meiotic division (MI) (Sherman et al., 2007; Allen et al., 2009). In elucidating the proximate causes of this sex bias of the risk factors, two different hypotheses have been put forward. According to one school of thought (Sherman et al., 2007; Allen et al., 2009), the protracted phase of MI arrest in women that lasts for several years makes the oocyte more vulnerable to NDJ than spermatozoa. An alternative to this explanation came from the study of NDJ in Drosophila (Zwick et al., 1999b), the organism that does not experience MI arrest. This line of thinking emphasized the meiotic drive of chromosomes and subsequent natural selection in asymmetric meiosis in females as the probable reasons of sex biasness of NDJ.
The association of advanced maternal age with DS birth is still an enigma. Although advanced maternal age is not the cause of NDJ, it is an obvious risk of DS birth. Apart from the studies on the higher incidence of DS birth at an advanced maternal age, the impact of maternal aging on the generation of aneuploid pregnancy was assessed in spontaneously aborted fetus and oocytes (Pellestor et al., 2003; Yusuf & Naeem, 2004). These studies suggested a steady rise in the proportion of trisomy conceptuses with increasing maternal age. To explain the age effect on the developing oocyte in relation to its decreasing efficiency to segregate homologous chromosomes properly, several hypotheses have been put forward. These include changes associated with the oocyte pool size, disturbance in ovarian hormone balance (Eichenlaub-Ritter & Boll, 1989; Gaulden, 1992; Warburton, 2005), sub-optimal operation of the spindle...