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~500 heteromorphism included
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How to cite this database: |
in
2023: 460 |
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last update: 01.
Jan. 2024 |
Created
by Dr. Thomas Liehr (PhD) |
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link helpful for diagnostics
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References
1. collect all available case reports on chromosomal heteromorphisms including euchromatic variants (EVs) and unbalanced chromosmal aberations (UBCAs) without (major) clinical signs and transmitted over generations;
here rather the number of variants reported than the number of cases in which they were seen, is in the focus.
2. provide information for cytogeneticists, patients and clinicians
For inversions see also Human Polymorphic Inversion DataBase
The word "heterochromatin" was introduced in 1928 by Emil Heitz {86}.
Euchromatic variants and (EVs) and unbalanced chromosmal aberations (UBCAs) without (major) clinical signs and transmitted over generations were highlighted specifically by John Barber {71}.
Heteromorphisms are copy number variantions (CNVs - loss or gain) of genetic material, which are so large that they can be visualized in the microscope. These heteromorphisms can be heterochromatic or euchromatic {1}.
CNVs can also be submicrocopic and are a big topic in molecular genetics, as well {1; http://dgv.tcag.ca/dgv/app/home}. Even though submicroscopic CNVs can also be hetero- or euchromatic, only euchromatic CNVs can be characteirzed at present by array-comparative genomic hybridization or sequencing.
Heteromorphisms were recognized shortly after chromosomes were analyzable systematically in the microscope and C-banding and NOR-staining were developed {2}.
Unfortunately heteromorphisms as well as CNVs are not treated equally; i.e. if a CNV or heteromorphism is rare and/or large it is mentioned in clinical reports. If it is well-known and/or frequent there is a tendency not to mention in a report.
Frequencies of heteromorphisms are not well known by now. There are differences in human subpoplulations - but these are not (well) documented {1}.
A small study in 2017 showed no difference in frequency of heteromorphisms in naturally concieved and ICSI/IVF-children {84},
The practical meaning of heteromorphisms (acc. to {1}) is that the may be helpful to:
- determine paternity
- differentiate between mono- and dizygote twins
- determine parental origin of additional and/or derivative chromosomes or of haploid sets in triploidy and chimeras
- detect maternal contamination in amniotic fluid cell cultures
- follow up bone marrow transplantation
- find genetic linkage.
Also there are reports on heteromorphims appearing in mosaic, which were interpeted as mitotic chromosomal evolution rather than chimerism {1, page 46}.
In literature from the 1980s it was already shown that heterochromatic repetitive sequences of the genome are translated to RNA in embryogenesis and also in tumors (reviewed in {1}). This is at present redicovered (e.g. {88; 89}).
It must be stressed that heterochromatic CNVs can not be vizualized equally using different staining or banding techniques and
that standards what a heteromorphism are not existant apart from some suggested in {1}.
A nice example is provided in a paper from 1972, where heteromorphisms were summarized for flourescent Q-banding (not for GTG-banding!)
and reported for pericentric regions of chromosomes 1, 3, 4, 9, 13, 14, 15, 16, 21 and 22 in two patient groups studied in two different labs,
There they evaluated using two different evaluation schemes concerning what is a heteromorphism. So there were different frequencies found.
Interestingly, heteromorphisms for chromosome 9 were only seen in one lab, and present in 0.28% of the cases {87}.
Accordingly, an indian study from 2022 {115} reporting heterochromatin extension for 10.11% for women with primary amenorrhea in a small study (178 females) is at least misleading. This range is the normally to be observed one for all humans - especailly, as there is no uniform agreement what size of heterochromtin is 'normal' at each chromosome, and also as no ethnically fitting control group was included.
As already discussed in early times of cytogenetics, it is ina paper from 2020 stressed again that heteromorphisms are more frequently observed in patients with reproductive failure {94}.
Repetitive elements evolve more quickly than euchromatic parts. Now it is also known that repetitive DNA contributes also to non-coding RNAs.
Interstingly, recently non-coding DNA could be shown to differ between Neanderthal, Denisovan and modern human and also that the different DNA-stretches have regulatory consequences {95}.
Review on repetitive elements see {106} and detectability see {107}.
Finally, in 2021 the since 20 years missing 8% of the human genome = repetitive elements and heterochromatic regions, were sequenced and are published {108}.
Also, special attention was given to the centromeres {108; 109} and their sizes deterimined in one person - as previosuly done ~50 years ago, as summarized in {1}.
Still, there is a a tendcy in literature to mix up subbands comprising (alpha-)satellite DNA, which cannot be sequenced properly, and the adjacent regions, being much more complex than unraveled, yet {116}.
On the other hand, the mentioned progress also leads to the insight that variance rather the rule and not uniformity of a 'standard reference sequence' {120}.
This page is organized like the 'sister-page' on small supernumerary marker chromosomes (sSMC)
- the structure is explained here.
However, here not the number of reported cases is documented, but the different variants.
Also take care that the nomenclature here is not always done acc. to ISCN !!
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