MEDICAL BIOLOGY, ANATOMY, HUMAN PHYSIOLOGY AND PATHOLOGY - Ya.I. Fedoniuk 2010

BIOLOGY

SECTION 1. BIOLOGICAL BASES OF HUMAN VITAL ACTIVITY

1.4. ONTOGENETIC LEVEL OF LIFE ORGANIZATION

1.4.2. Basics of human genetics

Chromosomal Mutations

Chromosomal mutations (chromosomal rearrangements, aberrations) are caused by changes in Chromosome Structure. Some of these mutations alter chromosome Morphology to such an extent that they can be observed under a Light Microscope in metaphase plates. The mechanisms underlying chromosomal mutations vary, but in all cases, a chromosome break occurs with the potential reunion of fragments. The following chromosomal

rearrangements are distinguished: deletions, duplications, inversions, and translocations. Deletion is the loss of a chromosome segment. Duplication is the doubling of a chromosome segment. Inversion is the rotation of a chromosome segment by 180°. Deletions and duplications lead to changes in Gene dosage. Inversions alter The sequence of gene arrangement within the inverted segment (Fig. 1.79).

Class="center">a b с d e f - normal

a b с e f - deletion of segment d

a b с d d e f - duplication of segment d

a b e d с f - inversion of segment c d e

Fig. 1.79. Diagram illustrating types of chromosomal rearrangements.

Translocation is the relocation of a chromosome segment to another position on the same chromosome (intrachromosomal translocations) or, most commonly, to another chromosome (interchromosomal translocations). A symmetrical translocation occurs when the centric region (containing the centromere) of one chromosome joins with the acentric fragment (lacking a centromere) of another. An asymmetrical translocation involves the fusion of centric regions with centric regions, and acentric regions with acentric regions. Centric fusion is one of the most common types of chromosomal rearrangements in humans, resulting in The formation of Chromosomes with two or three centromeres (dicentrics, tricentrics). Robertsonian translocation is the centric fusion between the long arms of acrocentric chromosomes. This is precisely how the translocation form of Down syndrome arises (translocation of an extra chromosome 21 onto one of the chromosomes of group D or G). Ring chromosomes, which are closed in the form of a ring, arise from the fusion of the arms of a chromosome that has lost its telomeres. Horizontal division of the centromere yields monocentric chromosomes with two genetically identical arms—isochromosomes. To predict offspring prognosis, it is essential to determine the specific type of mutation, which is achieved by analyzing the karyotype of the patient and their parents.

Rules for Recording Normal and abnormal human karyotypes:

1. At the very beginning of the genetic karyotype formula, the total number of chromosomes is indicated, followed by the COMPOSITION OF THE sex chromosomes. For example: 46, XX - normal female karyotype; 46, XY - normal male karyotype; 47, XXY - male karyotype with Klinefelter syndrome; 45, XO - female karyotype with Turner syndrome.

2. An additional autosome is designated by its respective number and the "+" sign. The notation 47, XY, +21 indicates a male karyotype with an extra chromosome 21 (Down syndrome). The loss of an entire chromosome is denoted by "-". Thus, the notation 45, XY, -21 indicates a male karyotype with monosomy of chromosome 21.

3. Chromosome arms are designated as "p" (short arm) and "q" (long arm).

4. Translocation is designated by "t" with specification in parentheses. For example: 45, XX, t (14;21)

- female carrier of a balanced 14/21 translocation.

5. Mosaicism is designated by a fraction. The formula 45, XO/46, XX indicates a female mosaic for Turner syndrome.

Human Chromosomal Disorders are associated with structural chromosomal abnormalities:

1) cri-du-chat syndrome (5p-) - deletion of the short arm of chromosome 5: multiple developmental anomalies combined with abnormal laryngeal development, causing the child's cry to resemble a cat's meow;

2) Orbeli syndrome (13q-) - deletion of the long arm of chromosome 13: microcephaly (small Brain size), broad nasal bridge, protruding upper jaw, ptosis (drooping eyelid).