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Karyotype




A karyotype is the observed characteristics (number, type, shape etc) of the chromosomes of an individual or species.

In normal s, and may be used to determine other macroscopically visible aspects of an individual's Genotype , such as Sex . In order to be able to see the chromosomes and determine their size and internal pattern, they are chemically labeled with a dye ("stained"). The pattern of individual chromosomes is called chromosome banding, whereas the study of whole sets of chromosomes is known as '''karyology'''.

Normal human karyotypes contain 22 pairs of autosomal chromosomes and one pair of Sex Chromosomes . Normal karyotypes for Women contain two X Chromosome s and are denoted 46,XX; Men have both an X and a Y Chromosome denoted '''46,XY'''. However, some individuals have other karyotypes with added or missing sex chromosomes, including 47,XYY , 47,XXY , 47,XXX and 45,X . The karyotype 45,Y does not occur, as an embryo without an X chromosome cannot survive.


TYPES OF BANDING

Molecular genetics employs several techniques to visualize different aspects of chromosomes:
  • G-banding is obtained with Giemsa stain following digestion of chromosomes with Trypsin . It yields a series of lightly and darkly stained bands - the dark regions tend to be heterochromatic, late-replicating and AT rich. The light regions tend to be euchromatic, early-replicating and GC rich. This method will normally produce 300-400 bands in a normal, human genome.

  • R-banding is the reverse of G-banding (the R stands for "reverse"). The dark regions are euchromatic (guanine-cytosine rich regions) and the bright regions are heterochromatic (thymine-adenine rich regions).

  • C-banding: Giemsa binds to Constitutive Heterochromatin , so it stains Centromere s.

  • Q-banding is a Fluorescent pattern obtained using quinacrine for staining. The pattern of bands is very similar to that seen in G-banding.

  • T-banding: visualize Telomere s.


probed for the Alu Sequence using FISH .]]


CLASSIC KARYOTYPE

In the "classic" (depicted) karyotype, a Dye , often Giemsa ''(G-banding)'', less frequently Quinacrine , is very used to stain bands on the chromosomes. Giemsa is specific for the Phosphate groups of DNA . Quinacrine binds to the Adenine - Thymine -rich regions. Each chromosome has a characteristic banding pattern that helps to identify them; both chromosomes in a pair will have the same banding pattern.

Karyotypes are arranged with the short arm of the chromosome on top, and the long arm on the bottom. Some karyotypes call the short and long arms ''p'' and ''q'', respectively. In addition, the differently stained regions and sub-regions are given numerical designations from Proximal to Distal on the chromosome arms. For example, Cri Du Chat syndrome involves a deletion on the short arm of chromosome 5. It is written as 46,XX,5p-. The critical region for this syndrome is deletion of 15.2, which is written as 46,XX,del(5)(p15.2).1


SPECTRAL KARYOTYPE (SKY TECHNIQUE)


Spectral karyotyping is a molecular Cytogenetic technique used to simultaneously visualize all the pairs of Chromosome s in an organism in different colors. Fluorescent ly-labeled probes for each chromosome are made by labeling chromosome-specific DNA with different Fluorophore s. Because there are a limited number of spectrally-distinct fluorophores, a combinatorial labeling method is used to generate many different colors. Spectral differences generated by combinatorial labeling are captured and analyzed by using an Interferometer attached to a fluorescence microscope. Image processing software then assigns a Pseudo Color to each spectrally different combination, allowing the visualization of the individually colored chromosomes.E. Schröck, S. du Manoir, T. Veldman, B. Schoell, J. Wienberg, M. A. Ferguson-Smith, Y. Ning, D. H. Ledbetter, I. Bar-Am, D. Soenksen, Y. Garini, T. Ried. Multicolor spectral karyotyping of human chromosomes. ''Science'', 26 July 1996 ; 273 (5274):494. abstract

This technique is used to identify structural chromosome aberrations in cancer cells and other disease conditions when Giemsa banding or other techniques are not accurate enough.


CHROMOSOME ABNORMALITIES

See Also: Chromosome abnormalities


Chromosome abnormalities can be numerical, as in the presence of extra or missing chromosomes, or structural, as in Translocations , Inversions , large-scale deletions or duplications. Numerical abnormalities, also known as Aneuploidy , often occur as a result of Nondisjunction during Meiosis in the formation of a Gamete ; Trisomies , in which three copies of a chromosome are present instead of the usual two, are common numerical abnormalities. Structural abnormalities often arise from errors in Homologous Recombination . Both types of abnormalities can occur in gametes and therefore will be present in all cells of an affected person's body, or they can occur during Mitosis and give rise to a Genetic Mosaic individual who has some normal and some abnormal cells.

Common chromosomal abnormalities that lead to disease include:

  • Turner Syndrome results from a single X chromosome (45, X or 45, X0).

  • Klinefelter Syndrome , the most common male chromosomal disease, otherwise known as 47, XXY is caused by an extra X on sex chromosome 23.

  • Edwards Syndrome is caused by Trisomy (three copies) of chromosome 18.

  • Down Syndrome , a common chromosomal disease, is caused by trisomy of chromosome 21.

  • Patau Syndrome is caused by trisomy of chromosome 13.

  • Also documented are trisomy 8, trisomy 9 and trisomy 16, although they generally do not survive to birth.


Some disorders arise from loss of just a piece of one chromosome, including

  • Cri Du Chat (cry of the cat), from a truncated short arm on chromosome 5. The name comes from the babies' distinctive cry, caused by abnormal formation of the larynx.

  • 1p36 Deletion Syndrome , from the loss of part of the short arm of chromosome 1.

  • Angelman Syndrome – 50% of cases have a segment of the short arm of chromosome 15 missing.


Chromosomal abnormalities can also occur in Cancer ous cells of an otherwise genetically normal individual; one well-documented example is the Philadelphia Chromosome , a translocation mutation commonly associated with Chronic Myelogenous Leukemia and less often with Acute Lymphoblastic Leukemia .


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