Chromosome Disease(Chromosomal Disorders)

By Live Dr - Sun Jan 11, 1:15 pm

As the organizational units for nuclear DNA, chromosomes are responsible for transporting hereditary information. Thus, changes in chromosomes-in their number or structure-can have serious clinical consequences–Chromosome Disease. Chromosome Disease:An abnormal condition due to an abnormality (in their  number or structure) of the chromosomes. The general features in autosome abnormalities are a triad of growth retardation, mental retardation, and specific somatic abnormalities. Changes of sex chromosome also have the abnormalities and malformations of internal or external genital organs. Down syndrome is a genetic disorder

Cytogenetics is the study of normal and abnormal chromosomes. This includes examination of chromosome structure, learning and describing the relationships between chromosome structure and phenotype, and seeking out the causes of chromosomal abnormalities.

Karyotype and Karyotype analysis

The karyotype is a photograph of all of the chromosomes of an individual cell; the term covers the number and structure of the chromosomes.


Somatic cells have two copies of each of 22 autosomes and either one X- and one Y-chromosome or two X-chromosomes  they are said to be  “diploid” (from the Greek for “double”).A somatic cell has 46 chromosomes.


Cytogenetic analyses are almost always based on examination of chromosomes fixed during mitotic metaphase. During that phase of the cell cycle, DNA has been replicated and the chromatin is highly condensed. The two daughter DNAs are encased in chromosomal proteins forming sister chromatids, which are held together at their centromere. The centromere is the structure where the mitotic spindle attaches prior to segregation. The centromere divides the chromosome into a short arm designated p and long arm designated q.

Metaphase chromosomes differ from one another in size and shape, and the absolute length of any one chromosome varies depending on the stage of mitosis in which it was fixed. However, the relative position of the centromere is constant, which means that that the ratio of the lengths of the two arms is constant for each chromosome. This ratio is an important parameter for chromosome identification, and also, the ratio of lengths of the two arms allows classification of human chromosomes into three basic morphologic types:

Chromosomes are Metacentric(1, 3, 16, 19, 20) if the centromere lies in the middle of the chromosome, submetacentric (2, 4-12, 17, 18, X) when the centromere is distant from the centre, and Acrocentric (13-15, 21, 22, Y) when the centromere lies near the end of the chromosome.

Karyotype analysis: arranging the chromosomes of a cell into a karyotype, then analysis.

Arranging the chromosomes of a cell in pairs(homologous chromosomes)from autosome 1 to autosome 22 that decrease in size as the numerical identification get bigger, and X and Y chromosomes are also identified.

Similar chromosomes inherited from different parents are known as homologous chromosomes, with corresponding homologous chromatids.  These chromosomes are similar in that they have the same genes at the same locations on the chromosome, but may have different forms (or alleles) of those genes.

The illustration shows an example of a karyotype. There are 22 pairs that decrease in size as the numerical identification gets bigger. Two X chromosomes are also displayed and therefore the sex status can be determined. It’s a female.

Karyotypes are presented in a standard form. First, the total number of chromsomes is given, followed by a comma and the sex chromosome constitution. 46, XX; 46, XY.

Binding Karyotype

Karyotypes mentioned above are no-banding karyotypes. Only according to centromere position and arm ratios, we can not identify specific pairs of chromosomes, because several or many pairs of chromosomes appear identical by these criteria. The ability to identify specific chromosomes with certainty was revolutionized by discovery that certain dyes would produce reproducible patterns of bands when used to stain chromosomes. Chromosome banding has since become a standard and indispensible tool for cytogenetic analysis, and several banding techniques have been developed:

Q banding: chromosomes are stained with a fluorescent dye such as quinacrine mustard. By Fluorescence microscopy, we can see there are bright and dim bands along the length of the chromosomes.

G banding: produced by staining with Giemsa after digesting the chromosomes with trypsin. Dark and light bands along the length of the chromosomes.

R banding: Heated and treated with KOH, then stained with Giemsa. Dark and light bands reversed to G bands.

Each of these techniques produces a pattern of dark and light (or fluorescent versus non-fluorescent) bands along the length of the chromosomes. Importantly, each chromosome displays a unique banding pattern, analogous to a “bar code”, which allows it to be reliably differentiated from other chromosomes of the same size and centromeric position.

It is important to note that new molecular techniques such as Fluorescence In Situ Hybridization (FISH) are now replacing some of the more traditional staining methods because of the limitations of the light microscope. These new techniques enable visualization of small duplications, deletions, or rearrangements that can no be seen with traditional cytogenetics.

Chromosome Labeling

Multiple parts of a chromosome are labeled. First, the chromosome itself is numbered. The autosomes, or chromosomes that are not involved in determining sex, are labeled 1-22 based on size from longest to shortest. Chromosomes that determine sex are labeled X or Y. Then, the chromosome is divided into the p and q arm regions. Each arm is then divided into sub-regions which are identified with a number. Finally, each sub-region is divided into bands identified with a number.

For example, Xq28, X chromosome, long arm, second region of the chromosome, the eighth band of that region.

Chromosomal Aberration

Chromosomal aberration includes numerical abnormality and structural aberration. Some aberrations occur spontaneously, and some are induced by ionizing radiation or chemical mutagen Etc.

Numerical Abnormality

Numerical aberration is a change in the number of chromosomes from the normal number characteristic of the human beings.

Haploid: A set of chromosomes containing only one member of each chromosome pair. The sperm and egg are haploid and, in humans, have 23 chromosomes. 22+X, 22+Y

Diploid: The number of chromosomes in most cells of the body. This number is 46 in humans. It is naturally twice the haploid number of 23 chromosomes contained in human eggs (ova) and sperm. 44+XX, 44+XY.

Euploidy is the condition of having a normal number of structurally normal chromosomes. there are normally 2 sets of 23 chromosomes or 46 total chromosomes in cells.  Euploid human females have 46 chromosomes (44 autosomes and two X chromosomes).

Two types of Numerical Abnormality: Polyploidy and Aneuploidy.

Polyploidy is the presence of three or more complete sets of chromosomes in a cell.

There are two main types of polyploidy, triploidy and tetraploidy.

Triploidy is the presence of three sets of chromosomes. This means that the total number of chromosomes in a triploidy cell would be 69.

Because of such an extreme difference in the amount of genetic material as compared to normal, cases of triploidy have severe effects. Babies with triploidy (referred to as triploidy syndrome) are usually lost through miscarriage. The rare triploid that survives for more than a few hours after birth is almost certainly a mosaic, having some cells with a normal number of chromosomes (46 chromosomes) and some cells with the extra set (69 chromosomes).

Mosaics are animals that have more than one genetically-distinct population of cells. For example, in a human mosaic, some of the cells might be 46, XX and some 47, XXX.

Causes of Triploidy

Diandry: fertilization of 1 oocyte by 2 spermatozoa.

Digyny: Fertilization of a diploid ovum by a sperm, which results in a triploid zygote.

Tetraploidy is the presence of four sets of chromosomes or 92 chromosomes total. Babies with tetraploidy have an even rarer chance of surviving birth.

Causes of Tetraploidy

Endoreduplication is an important variant of the eukaryotic cell cycle in which successive S phases follow each other without cell division. This leads to successive doublings of the nuclear DNA content.

Endomitosis: Chromosomal replication without nuclear division that results in cells with 4 copies of the same chromosome.

Aneuploidy is the presence of an additional or missing individual chromosome.

There are two main types of Aneuploidy, monosomy and trisomy.

Monosomy is the presence of only one copy of any chromosome. An individual having only one chromosome 6 is said to have monosomy 6. Loss of autosomes is not tolerated, is lethal. A common monosomy seen in many species is X chromosome monosomy, also known as Turner’s syndrome.

Trisomy is the presence of only three copy of any chromosome. It is found more commonly than Monosomy, and trisomy of sex chromosome is more commonly than autosomes. A common autosomal trisomy in humans in Down syndrome, or trisomy 21, in which a person has three instead of the normal two chromosome 21s.

Causes of Aneuploidy

Chromosome non-disjunction(Meiotic non-disjunction and Mitotic non-disjunction) and Chromosome loss

Meiotic non-disjunction arises from failure of paired homologous chromosomes or sister chromatid to disjoin at meiotic anaphase.

Nondisjunction, the failure of the chromosomes to disjoin and move to opposite poles may affect as many as 25% of all ova and 2% of all sperm. Half of these abnormal gametes are nullisomy, half are disomy. Two copies of a chromosome pass into the same gamete, leaving the other gamete as nullisomy. At fertilization the zygote formed from the gamete with nullisomy gets one copy of the chromosome from the gamete of the other parent and becomes monosomic for that chromosome. Monosomy for an autosome is not compatible with life. At fertilization, the zygote formed from the gamete with the two copies of the chromosome gets a third copy from the gamete of the other parent and become trisomic. As discussed earlier, most do not survive to term.

Mitotic non-disjunction arises from failure of sister chromatids to disjoin at mitotic anaphase.

Mitotic nondisjunction is one of the events that will produce a mosaic individual. When mitotic nondisjunction of chromosome 21 occurs early in development of a female, two new cell lines develop, 45, XX, -21 and 47, XX, +21, in addition to the 46,XX founding cells. The monosomy 21 cell line does not survive. The karyotype of the mosaic female is written 46, XX/47,XX + 21. Of course there is an equal probability for the mosaic to arise in a male. The severity of affected of mosaic individuals depends upon how early the nondisjunction occurred and what cell lines developed from those early embryonic cells.

Chromosome loss is the causality where a chromosome is missing from the new cell created via cell division. The chromosome delay in the cytoplasm and will be digested. Chromosome loss is another event which produces a mosaic individual.

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