Editing Cytogenetics (section)

==Human abnormalities and medical applications==
[[File:T922 CML.jpg|thumb|Philadelphia translocation t(9;22)(q34;q11.2) seen in chronic myelogenous leukemia.]]
Following the advent of procedures that allowed easy enumeration of chromosomes, discoveries were quickly made related to aberrant chromosomes or chromosome number.{{cn|date=February 2024}}

Constitutional cytogenetics: In some congenital disorders, such as [[Down syndrome]], cytogenetics revealed the nature of the chromosomal defect: a "simple" trisomy.  Abnormalities arising from [[nondisjunction]] events can cause cells with [[aneuploidy]] (additions or deletions of entire chromosomes) in one of the parents or in the fetus. In 1959, [[Jérôme Lejeune|Lejeune]]<ref>{{cite journal |last1=Lejeune |first1=Jérôme |last2=Gautier |first2=Marthe |last3=Turpin |first3=Raymond |title=Étude des chromosomes somatiques des neuf enfants mongoliens |trans-title=Study of somatic chromosomes from 9 mongoloid children |language=fr |journal=Comptes rendus hebdomadaires des séances de l'Académie des Sciences |date=16 March 1959 |volume=248 |issue=11 |pages=1721–1722 |pmid=13639368 |id={{NAID|10008406728}} |oclc=871332352 }}</ref> discovered patients with Down syndrome had an extra copy of chromosome 21. Down syndrome is also referred to as trisomy 21.

Other numerical abnormalities discovered include sex chromosome abnormalities. A female with only one X&nbsp;chromosome has [[Turner syndrome]], whereas a male with an additional X&nbsp;chromosome, resulting in 47 total chromosomes, has [[Klinefelter syndrome]]. Many other sex chromosome combinations are compatible with live birth including [[Trisomy X|XXX]], [[XYY syndrome|XYY]], and XXXX. The ability for mammals to tolerate aneuploidies in the sex chromosomes arises from the ability to [[Barr body|inactivate them]], which is required in normal females to compensate for having two copies of the chromosome. Not all genes on the X&nbsp;chromosome are inactivated, which is why there is a phenotypic effect seen in individuals with extra X&nbsp;chromosomes.{{cn|date=February 2024}}

Trisomy 13 was associated with [[Patau syndrome]] and trisomy 18 with [[Edwards syndrome]].{{cn|date=February 2024}}

Acquired cytogenetics: In 1960, Peter Nowell and David Hungerford<ref>Nowell PC, Hungerford DA. "A minute chromosome in human chronic granulocytic leukemia". pp. 1497–1501 in {{cite journal |title=National Academy of Sciences |journal=Science |date=18 November 1960 |volume=132 |issue=3438 |pages=1488–1501 |doi=10.1126/science.132.3438.1488 |pmid=17739576 }}</ref> discovered a small chromosome in the white blood cells of patients with [[Chronic myelogenous leukemia]] (CML). This abnormal chromosome was dubbed the [[Philadelphia chromosome]] - as both scientists were doing their research in [[Philadelphia, Pennsylvania]]. Thirteen years later, with the development of more advanced techniques, the abnormal chromosome was shown by [[Janet Rowley]] to be the result of a [[chromosomal translocation|translocation]] of chromosomes&nbsp;9 and 22. Identification of the Philadelphia chromosome by cytogenetics is diagnostic for CML. More than 780 leukemias and hundreds of solid tumors (lung, prostate, kidney, etc.) are now characterized by an acquired chromosomal abnormality, whose prognostic value is crucial. The identification of these chromosomal abnormalities has led to the discovery of a very large number of "cancer genes" (or [[oncogene]]s). The increasing knowledge of these cancer genes now allows the development of [[targeted therapies]], which transforms the prospects of patient survival. Thus, cytogenetics has had and continues to have an essential role in the progress of cancer understanding. Large databases ([[Atlas of Genetics and Cytogenetics in Oncology and Haematology]], [[COSMIC cancer database]], [[Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer]]) allow researchers and clinicians to have the necessary corpus for their work in this field.

===Advent of banding techniques===
[[Image:NHGRI human male karyotype.png|thumb|right|250px|Micrographic [[Karyotype|karyogram]] of a human male.]]
[[File:Human karyotype with bands and sub-bands.png|thumb|Schematic [[Karyotype|karyogram]] of a human, with annotated [[Locus (genetics)|bands and sub-bands]] as used in the [[International System for Human Cytogenomic Nomenclature]] for [[chromosomal abnormalities]]. It shows dark and white regions on [[G banding]]. It shows 22 [[homologous chromosome]]s, both the male (XY) and female (XX) versions of the [[sex chromosome]] (bottom right), as well as the [[human mitochondrial genetics|mitochondrial genome]] (at bottom left). {{further|Karyotype}}]]

In the late 1960s, [[Torbjörn Oskar Caspersson|Torbjörn Caspersson]] developed a quinacrine fluorescent staining technique (Q-banding) which revealed unique banding patterns for each chromosome pair. This allowed chromosome pairs of otherwise equal size to be differentiated by distinct horizontal banding patterns. Banding patterns are now used to elucidate the breakpoints and constituent chromosomes involved in [[Chromosomal translocation|chromosome translocations]]. Deletions and inversions within an individual chromosome can also be identified and described more precisely using standardized banding nomenclature. G-banding (utilizing trypsin and Giemsa/ Wright stain) was concurrently developed in the early 1970s and allows visualization of banding patterns using a bright field microscope.{{cn|date=February 2024}}

Diagrams identifying the chromosomes based on the banding patterns are known as ''idiograms''. These maps became the basis for both prenatal and oncological fields to quickly move cytogenetics into the clinical lab where karyotyping allowed scientists to look for chromosomal alterations. Techniques were expanded to allow for culture of free [[amniocyte]]s recovered from [[amniotic fluid]], and elongation techniques for all culture types that allow for higher-resolution banding.{{cn|date=February 2024}}

===Beginnings of molecular cytogenetics===
In the 1980s, advances were made in [[molecular cytogenetics]]. While radioisotope-labeled probes had been hybridized with [[DNA]] since 1969, movement was now made in using fluorescent-labeled probes. Hybridizing them to chromosomal preparations using existing techniques came to be known as [[fluorescence in situ hybridization|fluorescence ''in situ'' hybridization]] (FISH).<ref>{{cite book |last1=Gupta |first1=P. K. |title=Cytogenetics |date=2007 |publisher=Rastogi Publications |isbn=978-81-7133-737-8 }}{{page needed|date=October 2020}}</ref> This change significantly increased the usage of probing techniques as fluorescent-labeled probes are safer. Further advances in micromanipulation and examination of chromosomes led to the technique of [[chromosome microdissection]] whereby aberrations in chromosomal structure could be isolated, cloned, and studied in ever greater detail.{{cn|date=February 2024}}