Arranging chromosomes into a karyogram can simplify the identification of any abnormalities. Note that the banding patterns between the two chromosome copies, or homologues, of any autosome are nearly identical. Some subtle differences between the homologues of a given chromosome can be attributed to natural structural variability among individuals.
Occasionally, technical artifacts associated with the processing of chromosomes will also generate apparent differences between the two homologues, but these artifacts can be identified by analyzing 15—20 metaphase spreads from one individual.
It is highly unlikely that the same technical artifact would occur repeatedly in a given specimen. Today, G-banded karyograms are routinely used to diagnose a wide range of chromosomal abnormalities in individuals. Although the resolution of chromosomal changes detectable by karyotyping is typically a few megabases, this can be sufficient to diagnose certain categories of abnormalities. For example, aneuploidy , which is often caused by the absence or addition of a chromosome, is simple to detect by karyotype analysis.
Cytogeneticists can also frequently detect much more subtle deletions or insertions as deviations from normal banding patterns. Likewise, translocations are often readily apparent on karyotypes. When regional changes in chromosomes are observed on karyotypes, researchers often are interested in identifying candidate genes within the critical interval whose misexpression may cause symptoms in patients.
This search process has been greatly facilitated by the completion of the Human Genome Project , which has correlated cytogenetic bands with DNA sequence information. Consequently, investigators are now able to apply a range of molecular cytogenetic techniques to achieve even higher resolution of genomic changes. Fluorescence in situ hybridization FISH and comparative genomic hybridization CGH are examples of two approaches that can potentially identify abnormalities at the level of individual genes.
Molecular cytogenetics is a dynamic discipline, and new diagnostic methods continue to be developed. As these new technologies are implemented in the clinic, we can expect that cytogeneticists will be able to make the leap from karyotype to gene with increasing efficiency. Caspersson, T.
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Citation: O'Connor, C. Nature Education 1 1 Each chromosome pair viewed in a karyotype appears to have its own distinct "bar code" of bands. A chemical called colchicine is then applied to cells to arrest condensed chromosomes in metaphase. Cells are then made to swell using a hypotonic solution so the chromosomes spread apart. Finally, the sample is preserved in a fixative and applied to a slide. The geneticist then stains chromosomes with one of several dyes to better visualize the distinct and reproducible banding patterns of each chromosome pair.
Following staining, the chromosomes are viewed using bright-field microscopy. A common stain choice is the Giemsa stain. Giemsa staining results in approximately — bands of tightly coiled DNA and condensed proteins arranged along all of the 23 chromosome pairs. An experienced geneticist can identify each chromosome based on its characteristic banding pattern. In addition to the banding patterns, chromosomes are further identified on the basis of size and centromere location.
To obtain the classic depiction of the karyotype in which homologous pairs of chromosomes are aligned in numerical order from longest to shortest, the geneticist obtains a digital image, identifies each chromosome, and manually arranges the chromosomes into this pattern. At its most basic, the karyotype may reveal genetic abnormalities in which an individual has too many or too few chromosomes per cell.
Examples of this are Down Syndrome, which is identified by a third copy of chromosome 21, and Turner Syndrome, which is characterized by the presence of only one X chromosome in women instead of the normal two.
Geneticists can also identify large deletions or insertions of DNA. For instance, Jacobsen Syndrome, which involves distinctive facial features as well as heart and bleeding defects, is identified by a deletion on chromosome The sex of an unborn foetus can be determined by observation of interphase cells see amniotic centesis and Barr body.
Most but not all species have a standard karyotype. The normal human karyotypes contain 22 pairs of autosomal chromosomes and one pair of sex chromosomes. However, some individuals have other karyotypes with added or missing chromosomes, and in all such cases there are developmental abnormalities as a consequence. Karyotypes can be used for many purposes. Six different characteristics of karyotypes are usually observed and compared: [3]. A full account of a karyotype may therefore include the number, type, shape and banding of the chromosomes, as well as other cytogenetic information.
Variation is often found: 1. Levitsky seems to have been the first to define the karyotype as the phenotypic appearance of the somatic chromosomes, in contrast to their genic contents. Investigation into the human karyotype took many years to settle the most basic question: how many chromosomes does a normal diploid human cell contain? It took until the mid s until it became generally accepted that the karyotype of man included only 46 chromosomes. Although the replication and transcription of DNA is highly standardized in eukaryotes, the same cannot be said for their karotypes , which are highly variable between species in chromosome number and in detailed organization despite being constructed out of the same macromolecules.
In some cases there is even significant variation within species. This variation provides the basis for a range of studies in what might be called evolutionary cytology. Instead of the usual gene repression, some organisms go in for large-scale elimination of heterochromatin , or other kinds of visible adjustment to the karyotype.
A spectacular example of variability between closely related species is the muntjac, which was investigated by Kurt Benirschke and his colleague Doris Wurster.
The diploid number of the Chinese muntjac, Muntiacus reevesi , was found to be 46, all telocentric. The number of chromosomes in the karyotype between relatively unrelated species is hugely variable. The detailed study of chromosome banding in insects with polytene chromosomes can reveal relationships between closely related species: the classic example is the study of chromosome banding in Hawaiian drosophilids by Hampton Carson. In about 6, square miles, the Hawaiian islands have the most diverse collection of drosophilid flies in the world, living from rainforests to subalpine meadows.
These roughly Hawaiian drosophilid species are usually assigned to two genera Drosophila and Scaptomyza in the family Drosophilidae. The polytene banding of the 'picture wing' group, the best-studied group of Hawaiian drosophilids, enabled Carson to work out the evolutionary tree long before genome analysis was practicable. In a sense, gene arrangements are visible in the banding patterns of each chromosome.
Chromosome rearrangements, especially inversions , make it possible to see which species are closely related. The results are clear. The inversions, when plotted in tree form and independent of all other information , show a clear "flow" of species from older to newer islands. There are also cases of colonization back to older islands, and skipping of islands, but these are much less frequent. Using K-Ar dating, the present islands date from 0. The oldest member of the Hawaiian archipelago still above the sea is Kure Atoll, which can be dated to 30 mya.
The archipelago itself produced by the Pacific plate moving over a hot spot has existed for far longer, at least into the Cretaceous.
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