Human Developmental Biology. Danton Inc. O'Day

Чтение книги онлайн.

      Figure 4.1. A fertilized egg showing two polar bodies (false colored blue) and the fusing pronuclei (false colored green).

      As shown in Figure 4.1., the fusing haploid pronuclei (false coloured green in right panel) are seen in the centre of the egg while the two released pronuclei (false coloured blue in right panel) that resulted from the meiotic divisions are situated outside the egg. Sometimes a third polar body is observed which is due to the division of the first polar body. To reiterate, the polar bodies have no known developmental function other than to reduce the genetic complement of the egg without causing a large reduction in the egg cytoplasm. The zona pellucida (dark wide circular material outside the egg) surrounds the egg and polar bodies.

      Meiosis and Genetic Abnormalities: Non-Disjunction

      Non-Disjunction: With non-disjunction, the meiotic chromosomes don’t pull apart. As a result one cell gets both sister chromatids (that each will become a chromosome) while the other cell doesn't get that chromosome. Non-disjunction can occur during either meiosis I or meiosis II as illustrated in the following graphic (Figure 4.2). This figure summarizes how gametes can end up with one more or one less chromosome when non-disjunction occurs during meiosis.

      Figure 4.2. Non-disjunction during meiosis leads to abnormal chromosome numbers in developing eggs.

      The following points summarize the issue of non-disjunction:

      •Non-disjunction leads to abnormal chromosome numbers in eggs.

      •If one daughter gamete has an extra chromosome (i.e., 24 rather than the normal 23) the resulting syndrome is called trisomy (3 copies of the same chromosome will exist after fertilization) e.g., Down Syndrome—trisomy 21 is due to an extra copy of chromosome 21.

      •If the daughter gamete has 1 less chromosome (i.e., a total of 22 rather than the normal 23) it results in monosomy (e.g., Turner Syndrome—lacks a sex chromosome). Most cases of monosomy are not viable.

      Most cases of non-disjunction are due to the “maternal age effect”. Older women have higher incidences of abnormal chromosome numbers in their eggs due to those eggs being held in a meiotic block (prophase of meiosis I) for an extended period of time. Similarly older men can also produce sperm with abnormal chromosome numbers. This “paternal age effect” however cannot be due to meiotic block since it doesn’t occur in males.

      Trisomy 21—Down Syndrome

      Down syndrome is probably the most well known result from non-disjunction. As a result, Down syndrome individuals have an extra chromosome 21, hence the syndrome is also known as trisomy 21. Trisomy 21 affects the development of brain, immune system, heart and skeleton. Mental retardation is the constant hallmark of Down syndrome and individuals will typically develop early onset Alzheimer’s disease. Physically Down syndrome individuals have a broad face with a flat nasal bridge, wide set eyes and epicanthic folds (a skin fold on the upper eyelid). They also show a transverse crease in the palms of their hands. Often called a “simian crease”, the term is falling out of favor since “simian” refers to monkey or ape. Down syndrome occurs about once in every 700 births making it a common occurrence.

      Down Syndrome at the Molecular Level

      Trisomy 21 or Down syndrome is due to an extra copy of chromosome 21. Since these individuals have extra copies of certain genes this usually results in an excess production of certain proteins. The extra genes on chromosome 21 have many other functions and effects that are not all related to Down syndrome. However, a partial understanding of Down syndrome has come from studies of the genes encoded on chromosome 21. One of these gene is DSCR1 (Down Syndrome Critical Region 1) which encodes an inhibitory protein. While the role of the inhibitory protein DSCR1 in neuronal development is just one aspect of Down syndrome it does serve to exemplify how our understanding of this syndrome as well as many diseases is progressing