Medical Genetics - V. M. Zaporozhan 2005

Etiology of Hereditary Diseases
Types of mutations caused by changes in the number and structure of chromosomes
Genomic mutations - Heteroploidy (aneuploidy)

This is the increase or decrease in the number of Chromosomes by 1, 2, or more. Types of heteroploidies include monosomy, nullisomy, and polysomies (tri-, tetra-, and pentasomies):

a) monosomy — the absence of a single chromosome (2n-1);

б) nullisomy — the absence of a single chromosome pair (2n-2);

в) trisomy — one extra chromosome (2n+1);

г) tetrasomy — two extra chromosomes (2n+2);

д) pentasomy — three extra chromosomes (2n+3).

Causes of Heteroploidy Formation

1. The most critical mechanism underlying this pathology is chromosome nondisjunction during mitosis or Meiosis. Chromosomes that should normally separate during Cell Division remain linked together and migrate to the same pole during anaphase. This can occur during mitotic division, but it is more commonly observed during meiosis. In humans, acrocentric chromosomes tend to be involved in nondisjunction more frequently. Every gamete with an extra chromosome is matched by another that lacks one. Following Fertilization by a gamete with a normal chromosome Complement, the zygote turns out to be either trisomic (possessing an extra chromosome) or monosomic (lacking a chromosome). Examples of chromosome nondisjunction across various pairs are provided below.

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Fig. 2.14. Karyotype of a triploid

Upon fusion with an ovum (23,X), this yields 47,XXY zygotes (Klinefelter syndrome) or 45,X zygotes (Turner syndrome).

Following fertilization by normal spermatozoa (23,X), 47,XXX zygotes (trisomy X) or 45,X zygotes (Turner syndrome) are formed. Fertilization by spermatozoa (23,Y) results in 47,XXY zygotes (Klinefelter syndrome) or 45,Y zygotes (a lethal mutation).

Currently, The Use of DNA markers makes it possible to determine the parental origin of a chromosome. Such studies have demonstrated that chromosome nondisjunction occurs more frequently during oogenesis. For instance, in the majority of Down syndrome cases, the extra 21st chromosome results from maternal meiotic I nondisjunction. Other cases are summarized in Table 2.4.

If chromosomes fail to disjoin during mitosis in the Cleavage stage or other phases of embryonic development, mosaics are formed.

2. Lagging of chromosomes during the anaphase of cell mitosis in the embryonic or Postembryonic period of ontogenesis. Lagging chromosomes fail to reach The Nucleus and are degraded by cytoplasmic Enzymes.

3. The loss of a centromere leads to The formation of acentric chromosomes, which are lost during cell division.

4. Aneuploidies can be inherited from parents with trisomy or monosomy. For example, childbirth has been reported in women with Down syndrome (men with Down syndrome are infertile) and X polysomy syndrome, as well as in men with Klinefelter syndrome and Y polysomy. The theoretical probability that a child will inherit an extra chromosome from a parent is 50%. However, it is actually lower (around 10%) due to the low viability of aneuploid embryos and the demise of most of them during the Embryonic period.

Table 2.4. Origin of meiotic disturbances leading to aneuploidy