Genetics and Fetal Development

There are three sources of chromosome abnormalities that occur during the course of pregnancy. Primarily during the formation of oocytes and spermatozoa during gametogenesis, during the course of fertilization with the fusion of the oocyte and the sperm and in the postzygotic period. The consequences of any kind of chromosome abnormality usually is on a preimplantation death, implantation failure, spontaneous abortion, stillbirth or an infant born with birth defects.
15% of the population identified in a clinically identified pregnancy spontaneously aborts of which 60-70% are due to chromosome abnormalities. We have now begun to define the incidence of chromosome abnormalities prior to the third week of gestation and have found surprisingly that a significant number of pregnancies are lost following implantation. It is estimated that as many as 70% of all conceptions that are identified through in vitro fertilization programs, for example, may be carrying a chromosome abnormality. The significance of that is such that one of my colleagues remarked that "it is a miracle that any one of us is in this room." Following the 12th week of pregnancy, in the second and third periods of gestation, the incidence of stillbirths may be 5-10% and again chromosome abnormalities play a significant role in each of these stages.
There are three classes of chromosome abnormalities that we will briefly discuss with you. Aneuploidy which is defined as a gain or loss of single whole chromosomes. Polyploidy in which you have an additional set or sets of chromosomes. In the human, the chromosome complement consists of 23 different kinds of chromosomes so we have speak of triploidy with 69 chromosomes and tetraploidy with 92 chromosomes. Then there are instances where chromosomal rearrangements occur. The chromosomes physically break and heal or restitute in new forms or arrangements.
This is a normal karyotype in which to emphasize to you that indeed there are 46 chromosomes, 22 pairs of non-sex chromosomes or autosomes and an X and a Y constituting a male. It is possible for us using various kinds of stains to identify not only individual chromosomes from one another, but gains and losses of specific segments of chromosomes as well. Then you are looking at what constitutes G-banding in which they use trypsin and a Giemsa staining.
In the case of aneuploidy, and the next set of slides will briefly illustrate each of the classes of chromosome aberrations, there are three chromosomes and the total count is now 47 instead of the normal number of 46. This is the characteristic karyotype associated with trisomy 21 in which there is in all of the cells presumably an extra chromosome 21.
Triploidy. Each chromosome is represented 3 times throughout the entire complement and so the total chromosome number is 69 and this is an example of polyploidy. Another example of polyploidy is shown in this lower segment in which the total chromosome count is 92, an example of tetraploidy. Each chromosome has its own particular pair. Tetraploidy characteristically arises after the first postzygotic cleavage in which the chromosomes divide but the cytoplasm does not, so the chromosome number immediately goes from 46 to 92. The cell fails to divide, to form two daughter cells. You still have only one parental cell remaining but now the chromosome number has been immediately doubled. Invariably, this will lead to a missed abortion early in the first trimester although again, for all of the statements we make, there are exceptions. There have been a few, a small number of examples of diploid, tetraploid mosaic infants born with birth defects presumably associated with the fact that a portion of their cells now have a doubling of their chromosome number.
Breakage of the chromosome at two particular sites on either of the two arms and the broken ends of the long part healing and forming this ring. It also means, of course, that pieces or segments of genetic material have been lost in the formation of this ring chromosome thereby leading to chromosome and genetic imbalance and will be associated with either spontaneous abortions, stillbirth or an infant born with a genetic abnormality.
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