An Introduction to chromosomes:

The ability of the chromosomes in getting stained reveals the true nature of the chromosome (derived from the Greek work word. The word chroma indicates color). These stainable bodies appear like threads under a microscope. They contain the genetic material, mainly the DNA coiled around the proteins. Human chromosomes are visible with when the cell is undergoing mitotic or meiotic cell division. There are total 46 chromosomes in each human cell.

· Autosomes: There are total 44 autosomes or 22 pairs. Each pair consists of homologous chromosomes. In a pair, one chromosome comes from the father and the other chromosome comes from the mother.

· Sex Chromosomes: There are two different types of sex chromosomes, X and Y respectively.

The average size of the human metaphase chromosome is 5 millimeters. Chromosomes tightly coil and get condensed during metaphase. Chromosomes appear in different shapes during each phase of the cell cycle. They appear thread-like during interphase. During metaphase, chromosomes look like rod-shaped. They look like V, J or rod-shaped during anaphase. Von Hartz coined the term chromosome. The scientists who first discovered the structure of chromosomes were Schleiden, Virchow, and Bütschli. Walter Sutton and Theodor Boveri independently developed the chromosome theory of inheritance in 1902.

An interphase nucleus contains strands of a material called chromatin. There are two regions in the chromatin, mainly coiled and extended regions.

· Heterochromatin: It is the dark staining area of the chromatin. There are two types of heterochromatin. Constitutive heterochromatin contains repetitive sequences. It is present near the centromere. Constitutive heterochromatin never expresses itself. There is one more type of heterochromatin, known as facultative heterochromatin, which expresses itself.

· Euchromatin: It is the light staining area of the chromatin.





The chief constituent of chromatin is DNA, the blueprint of life. At the time of cell division, chromatin strands coil into compact structures, so that they easily fit into the cell nucleus. Chromosomes appear as thick rods only during the cell division. They uncoil and form chromatin at the end of cell division.









Image: Human chromosomes revealed through karyotyping





Structure of the chromosome:

Metaphase chromosome appears clearly under the microscope. Following are the principal point to be discussed:

· Chromatids: Each metaphase chromosome consists of two symmetrical halves parallel to each other. They are called chromatids. These chromatids are present in the form of chromonema during prophase. There are two types of chromatids mainly, sister and non-sister chromatids. Two chromatids are present on a single chromosome. Thus they are called sister chromatids. The concept of dyad describes a pair of sister chromatids. These structures join with the help of a centromere. Non-sister chromatids are either of the two chromatids of a chromosome pair.

· Centromere: A centromere is a light staining constricted area to which both the chromatids are attached. A centromere divides the chromatids into short and long arms respectively. The short arm is known as “p” arm. The long arm is known as “q” arm. Centromere produces a primary constriction. It is the position of the centromere. It is different for different chromosomes. Secondary constriction is also known as nucleolar organizer region. It is involved in the formation of the nucleolus. Human centromere consists of several hundred kilobases of repetitive DNA. Centromeres are the sites where spindle fibers are attached. Thus, centromere helps in the movement of the chromosome.

· Satellite: A satellite is a region that is attached to the chromosome by a thread of chromatin. It is present at the distal region of the arm of the chromosome.

· Telomere: A special DNA-protein complex is present at the ends of the chromosomes. This complex is known as a telomere, with tandem repeats of TTAGGG-3’ sequences between 3-20 kilobases in length. Telomeres are not genes since they do not code for any functional molecule. Telomeres provide structural stability to the chromosomes by sealing their ends. Telomeres protect the chromosomes from damage. They also protect the chromosome from fusing into a ring or binding to other DNA.





Classification of chromosomes:

1. Classification based on the position of the centromere:

· Metacentric: The two arms are almost equal in their lengths. The location of the centromere is at the center of the chromosome.

· Submetacentric: The two arms of the submetacentric chromosomes are unequal in length. The location of the centromere is slightly away from the center.

· Acrocentric: One arm of an acrocentric chromosome is short. Whereas, the other arm is long.

· Telocentric: A telocentric chromosome has only one arm.

2. Standard classification: It is also known as Denver classification. It classifies chromosomes into seven groups, depending on the length of the chromosomes.

· Group A: This group consists of pairs of chromosomes 1, 2 and 3. Chromosome 1 is the largest human chromosome. It represents 8% of the total DNA content. Chromosome 2 is the second one. The third chromosome represents 6.5 % of the total DNA content.

· Group B: This group consists of pairs of chromosome 4 and 5.

· Group C: This group consists of pairs of chromosome 6, 7, 8, 9, 10, 11 and 12.

· Group D: This group consists of pairs of chromosomes 13, 14 and 15.

· Group E: This group consists of pairs of chromosomes 16, 17 and 18.

· Group F: This group consists of pairs of chromosomes 19 and 20.

· Group G: This group consists of pairs of chromosomes 21 and 22.

· Sex Chromosomes: There are two types of sex chromosomes. X chromosome and Y chromosome are called sex chromosomes.

3. Paris nomenclature: According to this method, the long and short arms of the chromosomes have specific regions that get stained. These regions are further stained using banding techniques. Such techniques may not only help to identify specific chromosomes, but also find out the location within the chromosome. Banding techniques may help to detect minor structural abnormalities.





What is sex chromatin?

The nucleus in the interphase is in the resting phase. An interphase nucleus shows a dark stain chromatin mass attached on one side of the nuclear membrane. Sex chromatin is also known as the Barr body. It is observed only in females. However, the chromatin determination using the Barr body is not as accurate as the Karyotyping technique.





What are chromosomal aberrations?

Chromosomal mutations or aberrations are variation in the normal chromosome structure or chromosome number.

A deletion is a chromosomal mutation in which a part of a chromosome is missing. Chromosomal breaks result in deletions. Sometimes an entire chromosome may get deleted. Duplication may lead to doubling of a chromosomal segment. Excision of a chromosomal segment follows reinsertion leading to an inversion. A translocation is a chromosomal mutation in which a chromosome segment gets positioned in a different location in the genome.





Chromosome Analysis:

Chromosome analysis indicates a proper diagnosis of many clinical conditions. It is a microscopic analysis of chromosomes in the dividing cells. Chromosomal analysis can detect chromosome number and structure.

Uses of chromosome analysis are as follows:

· Detection of congenital malformations, mental retardation, and repeated abortions.

· Prenatal diagnosis

· Diagnosis of malignancies





Karyotyping:

Karyotyping is a test to evaluate the number and the structure of the chromosomes. In this procedure, the metaphase chromosomes are obtained and photographed. The procedure of karyotyping is specialized. Peripheral blood lymphocytes, bone marrow cells or amniotic fluid samples are collected and analyzed for chromosomes. A photo-micrograph reveals chromosomes scattered randomly. These chromosomes are arranged into groups, using the software. A karyotype can be sued to detect chromosomal abnormalities.





Chromosome Banding:

Analysis of chromosome becomes precise with the help of banding techniques. There are four types of banding techniques such as G-banding, Q-banding, R-banding, and C-banding. A unique pattern of light and dark bands are obtained using the G-banding technique.





Fluorescence in-situ hybridization (FISH):

FISH is a new diagnostic technique that involves a single-stranded probe annealing to its complementary sequence. FISH can be used to detect minute chromosomal aberrations, malignancies, and study of chromosomes.





References:

[1] Medical genetics, G.P. Pal

[2] Human Genetics, 3/e, Gangane

[3] Vogel and Motulsky's Human Genetics: Problems and Approaches, Friedrich Vogel, Gunter Vogel, Arno G. Motulsky

[4] Biology for the IB Diploma: Standard and Higher Level, Andrew Allott

[5] Principles of Medical Genetics, Thomas D. Gelehrter

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