Nondisjunction in Down's syndrome

Nondisjunction in Down's syndrome has been examined by a number of researchers in genetics in recent years with an eye to better understand the syndrome and to find a predictor of its development. Nondisjunction refers to the failure of homologous pairs of chromosomes to separate during the first meiotic division or of the two chromatids of a chromosome to split during anaphase of mitosis or the second meiotic division. The result of nondisjunction is an abnormal number of chromosomes in the daughter cells. Studies of this issue have been conducted in general terms and on specific chromosomes alike. They have been conducted in different parts of the world to see if there are different forces at work. The issue has also been examined from the standpoint of its consequences in the development of Down's Syndrome and other medical problems for mother and child.

Trisomy 21 is the genetic reference to Down Syndrome and is the most common cause of mental retardation. It is usually caused by meiotic nondisjunction, and studies have centered on nondisjunction of chromosome 21, which is usually studied by cytogenic heteromorphisms. Such studies suggest that the origin of the extra chromosome is paternal in some 20 percent of the case, but two large molecular studies, using multiple DNA polymorphisms along the long arm of human chromosome 21, points to paternal nondisjunction in only 5 percent of cases. The difference has been attributed to increased accuracy in the molecular

nformative for parental origin in almost all cases. The authors conclude that for some cases there may be a causal relationship between pericentromeric recombination and nondisjunction. Phillips, Cromwell, Rivas, Simpson, and Elias consider the issue of trisomy 21 and its maternal origin in terms of the maternal age of menopause, asking whether reproductive age rather than chronological age influences the risk of nondisjunction. The authors note first that the biological basis underlying the increased risk of nondisjunction in offspring of women of advanced maternal age is not understood at this time, and they propose to test the issue with the hypothesis that maternal reproductive age, meaning the distance in time from approaching menopause, rather than chronological age is pivotal in the etiology of nondisjunction. It is well known that trisomy in offspring increases with advancing maternal age. It has been proposed that hormonal changes at the end of the reproductive life span amy adversely affect maternal meiosis and predispose towards nondisjunction. The reasons for this hypothesis was the observation that reducing the reproductive lifespan in mice by unilateral oophorectomy produced a shift in the risk of aneuploidy t

Category: Medical - N