Origins of Aneuploidy
Victoria N. Torres
Biol 196L: 001
I present a commentary and lineation of three separate reports regarding the origin of T21 gametes leading to the anomaly of Down syndrome. Each study speculates as to the various etiologies of Down syndrome. One report investigates the parental age impact and determines that maternal nondisjunction is an important factor that occurs readily during meiosis I. A separate dissertation, a commentary on a former study, also examines the parental age effect, determining that both a maternal and paternal influence exist yet, the maternal age effect is more prominent. In my report, the evidence from the three research studies is presented such that all the factors outlined in the first two studies support the idea that the third report suggests: an accumulation of Trisomy 21 oocytes that are developed in utero.
The most commonly diagnosed mental/malformation disorder is Down syndrome which is caused by gene dosage-imbalance resulting from human chromosome-21 trisomy. In 1866, John Langdon Down was the first individual to classify and study these individuals sharing the same malformations and mental handicaps. It was noted that all the individuals with the chromosomal anomaly exhibited similar characteristic phenotypic malformations, cognitive impairment, and a tendency to develop Alzheimer’s and heart disease (Giriajan, 2009).
Different forms exist within the realm of Down Syndrome: 95% of the afflicted have complete trisomy (all cells in body are trisomic), approximately 1% have mosaicism (some cells in the body trisomic while others are normal), and approximately 4% have translocation (some parts or all of chromosome 21 is actually attached to another chromosome in the karyotype causing duplication of genetic material) (Giriajan, 2009).
The factors that may cause trisomy are varied and sometimes inconclusive. Speculations arise with the information that each new study brings, therefore factors are constantly evolving, changing, and branching off one another. Some of the most important factors being researched are delayed fertilization of oocytes and advancing parental age (Jyothy, 2001).
An early study attempted to explain the parental age effect that seemed to account for most instances of T21. It was hypothesized that the paternal age, in addition to maternal age might also have an impact on these instances. In this study, researchers also attempted to isolate the meiotic division during which the abnormality was most likely to occur. In doing so, the relationship between meiotic arrests and trisomy 21 were more readily linked to maternal ageing.
Although the parental age effect seems to be the most influential factor, yet another study also examined it and recognized inconsistent results in previous studies. They redressed the paternal age effect, in an attempt to negate previous inconclusive studies. Basing much of their study off of Penrose’s 1964 study on advancing maternal age, they also examined the impact of meiotic arrests that occur several times during the life of a female.
One very recent study hypothesized that the maternal age effect on the most common type of trisomy (complete trisomy) could be due to the accumulation of pre-existing trisomy 21 (T21) cells in ovaries of human females that are created during development from fetal life to adulthood.
Generalizations are frequently made about the origin of the trisomy 21 DNA mutation, primarily linking it to advanced maternal age subsequently resulting in inaccurate desegregation of initially normal disomic oocytes. As of late, it is argued that other factors may lead to the T21 genotype such as accumulation of aneuploid oocytes with increased age, as well as advanced paternal age. A 2001 study recognized common factors in trisomic births as being delayed fertilization, advanced maternal age, and mutagens that cause nondisjunction of initially viable oocytes. Out of a large sample, the average
