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Down syndrome birth: Impact of environmental risk factors on maternal meiotic errors
S K DEY,
Published in Nova Science Publishers, Inc.
2012
Pages: 121 - 148
Abstract
Down Syndrome (DS) is the most commonly identified genetic form of intellectual disability and is characterized by specific phenotypic disposition with set of congenital defects. Epidemiologic study of DS was initiated immediately after its discovery in mid 1800s and with the advent of karyotyping its etiology was identified. It is the triplication of human chromosome 21 (Ch21), that is the presence of an extra copy of Ch21, causes the typical phenotypic features of DS. The supernumerary Ch21 arises due to NDJ (NDJ) of the chromosome at anaphase of meiosis during parental gametogenesis. It is now estimated that nearly 95% of all live born DS have an extra copy of Ch21 due to meiotic NDJ, whereas other forms of DS namely, somatic mosaicism due to mitotic error in embryonic development and translocation of Ch21 account for the rest. For overwhelming majority of cases within the non disjoined category, 90% of the error arises in oocyte. It is probably the protracted phase of oogenesis that makes the women more susceptible to NDJ than their male partners. Detail epidemiologic and population based research have identified advanced maternal age and altered pattern of meiotic recombination as two risk factors that make the oocyte susceptible to acquire faulty number of chromosome. The birth prevalence study revealed a progressive increase in incidence of DS birth with advancing age of women and several hypotheses have been put forward to explain the maternal age effect on meiotic chromosome segregation system. STR (short tandem repeat) markers based genotyping of DS family demonstrated that ̃80% of maternal errors occur in first phase of meiosis, that is meiosis I (MI), and there is fall in usual recombination frequency on Ch21 that experience NDJ at MI. With chromosome mapping approach, workers have succeeded in identifying the erroneous placement of chiasmata on long arm of Ch21 that predispose the chromosome to mis-segregation. Refined analyses with large sample size have identified a potential interaction between maternal age and altered pattern of recombination.Beside maternal age and altered recombination, several habitual or environmental factors have been identified to associate with DS birth. This include, maternal habit of smoking, chewing tobacco and contraceptive pill, alcohol and coffee consumption, maternal exposure to radiation, low socio-economic livelihood etc. It seems almost certain that environmental risk factors for chromosome NDJ do exist, but not yet confirmed. With incisive approach to identify the relation among recombination, maternal age and environmental risk factors, workers have elucidated a complicated interaction among these three factors. Moreover, polymorphism of certain genes in folic acid metabolism pathway has been identified as predisposing to DS conception among the women. All these discoveries unequivocally suggest that the etiology of DS birth is complicated and multidimensional. In this review we will focus on the present understanding of the maternal risk factors of DS birth with brief description on recent developments in the field of Down syndrome research. Additionally, we will also discuss the future scope of research and their possible implication in designing the preventive measures.
About the journal
JournalNew Developments in Down Syndrome Research
PublisherNova Science Publishers, Inc.
Open AccessNo