Normal disjunction in meiosis I and meiosis II 

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... have been studying the aneuploids human conditions after the descrip- tion of the first case of trisomy 21 (Down syndrome) on 1959 by Lejeune and Patricia Jacob. They focused their investigation and studies on the genesis of this abnormal condition developed by humans. Recently, aneuploidy was also confirmed experimentally as a dominant mutator, independent of gene mutation in other eukaryotes, including Drosophila, yeast, plants, and mice. These studies were centered in searching about three basic things; the frequency of aneuploid conditions, the reason of gaining (extra) or loosing (less) chromosomes and the nondisjunctional mechanism that gives rise to aneuploid conditions. Despite the technological development and the number of realized studies in aneuploid genesis, investigators still don’t have clear answers to the second and the third interrogates, however the first one has been answered. The frequency of aneuploid conditions which is amazingly common and clinically important in our species is estimated in approximately 5% of clinically recognized pregnancies (1). Therefore we will try to re- combine all the results of previous studies, in order to reach a conclusion that defines the causes of chromosomal nondisjunction and answer the question wheather maternal age is its only trigger or there are still other factors behind it? Nondisjunction is the miss segregation of a homologous pair of chromosomes during meiosis (figure 1). It leads to the formation of a new cell with an abnormal amount of genetic material. A number of clinical condi- tions are the result of this type of chromosomal mutation. Homologous chromosomes are identical chromosomes that can be observed in pairs, in which 50 % of this amount is inherited from each parent. Humans have 46 chromosomes, or 23 homologous pairs. Normally, in meio- sis the homologous chromosomes attach to spindle fibers (figure 2), which connect the 2 centrioles and become aligned at the cell equator. Before the first meiotic division takes place the homologous pairs migrates to the cell ́s opposite poles by means of the pulling action of the spindle fibers, and upon meiosis completion each gamete will have one copy of every chromosome. However, this process can suffer some errors that lead to homologous chromosomes separation failure and thus both migrate to the same pole (figure 3). Consequently two types of gametes are produced, one of which has two chromosomal copies, whereas the other lacks one. A zygote which has a chromosome less than the normal diploid amount (2n-1) is called monosomic, and that which has an extra chromosome (2n+1) is trisomic, both conditions may develop severe abnormalities that can be fatal (1). Meiosis is a process that consists of a number of check points that regulate cell division in all its phases to ensure that the cells will divide and give rise to new ones correctly without any error. In case an error occurs these regulating points must correct it. One of these check points is the spindle fibers checkpoint which is responsible of three principle steps; formation of these spindle fibers, the attachment of chromosomes to them and the adequate segregation of these chromosomes. When any check point fails in realizing its correct function, it leads to nondisjunction, as a result of the incorrect segregation of the homologous chromosomes. Despite the insufficient studies about the causes of nondisjunction, it is known to occur more frequently in older cells. This is why older women may give birth to affect off springs due to an aneuploid abnormality more than young ones. The risk of a twenty- years-old mother giving birth to a child with Down syndrome is about one in two thousand and it increases to one in thirty in the case of a forty-five years old woman. This hypothesis depends on a simple elucidation that in older cells the regulating system does not function as in younger cells and as a consequence the cell will lose the control. Thus an older cell undergoing meiosis would be more likely than a younger one to ignore the constraints of the spindle checkpoint and hence give rise to aneuploid cells. This was confirmed by a study done in patients with Down syndrome which demonstrated that the incidence of this syndrome was elevated with increased maternal age. Many specialists recommend that women who become pregnant at age 35 or older must undergo prenatal testing for Down syndrome. The probability of pregnant fewer than 30 to give birth to a baby with Down syndrome is less than 1 in 1,000, but the chance of having a baby with Down syndrome increases to 1 in 400 in women who become pregnant at age 35. The likelihood of Down syndrome continues to increase as women ages do, so that by age 42, the chance is 1 in 60 and by age 49, the chance is 1 in 12. But using maternal age alone will not detect over 75% of pregnancies that result in Down syndrome (10). No disjunction doesn’t only relate with maternal conditions, but also with paternal and mitotic conditions. A study verified that trisomy 21 was 90.9% maternal, 4.5% paternal and 4.5% from a mitotic origin; similar to distributions reported previously (4). It also confirmed that nondisjunction doesn’t only take place in meiosis II but also in meiosis I (MI: 46.1%, MII: 53.9%).Even though it was established by other studies that MI is 70% and MII is 30% related to Down syndrome, it was reported that what causes it in 88% of cases is the extra copy of chromosome 21 derived from the mother, in 8% of the cases the father provided the extra copy of chromosome 21 and in the remaining 2% Down syndrome is due to mitotic errors; an error in cell division which occurs after fertilization when the sperm and ovum are joined (10). It was also reported in 82 patients with trisomy 13 that the parental origin was determined in every case and in 89% the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII errors (8). Until here we achieved to demonstrate that nondisjunction is from maternal, paternal and mitotic origin, the distinctive difference are the frequencies and percentages as we can see briefly in the table below. Adapted from Hall et al . (6). MI, meiosis I; MII, meiosis II; PZM, post-zygotic mitotic (11). The direct exposure to high levels of genotoxic gaseous and particulate substances from the engines combustion used in motor vehicles is required by certain type ...