Photographic display of total chromosome complement in a cell
"Idiogram" redirects here; not to be confused withideogram.
Akaryotype is the general appearance of the complete set ofchromosomes in the cells of aspecies or in an individual organism, mainly including their sizes, numbers, and shapes.[1][2]Karyotyping is the process by which a karyotype is discerned by determining the chromosome complement of an individual, including the number of chromosomes and any abnormalities.
Micrographic karyogram of human male usingGiemsa stainingSchematic karyogram demonstrating the basic knowledge needed to read a karyotype
Akaryogram oridiogram is a graphical depiction of a karyotype, wherein chromosomes are generally organized in pairs, ordered by size and position of centromere for chromosomes of the same size. Karyotyping generally combineslight microscopy andphotography in themetaphase of thecell cycle, and results in aphotomicrographic (or simply micrographic) karyogram. In contrast, aschematic karyogram is a designed graphic representation of a karyotype. In schematic karyograms, just one of the sisterchromatids of each chromosome is generally shown for brevity, and in reality they are generally so close together that they look as one on photomicrographs as well unless the resolution is high enough to distinguish them. The study of whole sets of chromosomes is sometimes known askaryology.
Karyotypes describe thechromosome count of an organism and what these chromosomes look like under a lightmicroscope. Attention is paid to their length, the position of thecentromeres, banding pattern, any differences between thesex chromosomes, and any other physical characteristics.[3] The preparation and study of karyotypes is part ofcytogenetics.
The basic number of chromosomes in thesomatic cells of an individual or a species is called thesomatic number and is designated2n. In thegerm-line (the sex cells) the chromosome number isn (humans: n = 23).[4][5]p28 Thus, in humans 2n = 46.
So, in normaldiploid organisms,autosomal chromosomes are present in two copies. There may, or may not, besex chromosomes.Polyploid cells have multiple copies of chromosomes andhaploid cells have single copies.
Chromosomes at various stages ofmitosis. Karyograms are generally made by chromosomes in prometaphase or metaphase. During these phases, the two copies of each chromosome (connected at thecentromere) will look as one unless the image resolution is high enough to distinguish the two.Micrograph of human chromosomes before further processing. Staining with Giemsa confers a purple color to chromosomes, but micrographs are often converted tograyscale to facilitate data presentation and make comparisons of results from different laboratories.[7]
The study of karyotypes is made possible bystaining. Usually, a suitabledye, such asGiemsa,[8] is applied aftercells have been arrested duringcell division by a solution ofcolchicine usually inmetaphase orprometaphase when most condensed. In order for theGiemsa stain to adhere correctly, all chromosomal proteins must be digested and removed. For humans,white blood cells are used most frequently because they are easily induced to divide and grow intissue culture.[9] Sometimes observations may be made on non-dividing (interphase) cells. The sex of an unbornfetus can be predicted by observation of interphase cells (seeamniotic centesis andBarr body).
Six different characteristics of karyotypes are usually observed and compared:[10]
Differences in absolute sizes of chromosomes. Chromosomes can vary in absolute size by as much as twenty-fold between genera of the same family. For example, the legumesLotus tenuis andVicia faba each have six pairs of chromosomes, yetV. faba chromosomes are many times larger. These differences probably reflect different amounts of DNA duplication.
Differences in the position ofcentromeres. These differences probably came about throughtranslocations.
Differences in relative size of chromosomes. These differences probably arose from segmental interchange of unequal lengths.
Differences in basic number of chromosomes. These differences could have resulted from successive unequal translocations which removed all the essential genetic material from a chromosome, permitting its loss without penalty to the organism (the dislocation hypothesis) or through fusion. Humans have one pair fewer chromosomes than the great apes. Human chromosome 2 appears to have resulted from the fusion of two ancestral chromosomes, and many of the genes of those two original chromosomes have been translocated to other chromosomes.
Differences in number and position of satellites.Satellites are small bodies attached to a chromosome by a thin thread.
Differences in degree and distribution ofGC content (Guanine-Cytosine pairs versusAdenine-Thymine). In metaphase where the karyotype is typically studied, all DNA is condensed, but most of the time, DNA with a high GC content is usually less condensed, that is, it tends to appear aseuchromatin rather thanheterochromatin. GC rich DNA tends to contain morecoding DNA and be moretranscriptionally active.[11] GC rich DNA is lighter onGiemsa staining.[12] Euchromatin regions contain larger amounts ofGuanine-Cytosine pairs (that is, it has a higherGC content). The staining technique usingGiemsa staining is calledG banding and therefore produces the typical "G-Bands".[12]
A full account of a karyotype may therefore include the number, type, shape and banding of the chromosomes, as well as other cytogenetic information.
Micrographic karyogram of a human male. See section text for details.Schematic karyogram of a human. Even at low magnification, it gives an overview of thehuman genome, with numbered chromosome pairs, its main changes during thecell cycle (top center), and themitochondrial genome to scale (at bottom left). See section text for more details.
Both the micrographic and schematic karyograms shown in this section have a standard chromosome layout, and display darker and lighter regions as seen onG banding, which is the appearance of the chromosomes after treatment withtrypsin (to partially digest the chromosomes) andstaining withGiemsa stain. Compared to darker regions, the lighter regions are generally moretranscriptionally active, with a greater ratio ofcoding DNA versusnon-coding DNA, and a higherGC content.[11]
Both the micrographic and schematic karyograms show the normal humandiploid karyotype, which is the typical composition of thegenome within a normal cell of the human body, and which contains 22 pairs ofautosomal chromosomes and one pair ofsex chromosomes (allosomes). A major exception to diploidy in humans isgametes (sperm and egg cells) which are haploid with 23 unpaired chromosomes, and thisploidy is not shown in these karyograms. The micrographic karyogram is converted intograyscale, whereas the schematic karyogram shows the purple hue as typically seen on Giemsa stain (and is a result of its azure B component, which stains DNA purple).[14]
The schematic karyogram in this section is a graphical representation of the idealized karyotype. For each chromosome pair, the scale to the left shows the length in terms of millionbase pairs, and the scale to the right shows the designations of thebands and sub-bands. Such bands and sub-bands are used by theInternational System for Human Cytogenomic Nomenclature to describe locations ofchromosome abnormalities. Each row of chromosomes is vertically aligned atcentromere level.
Based on the karyogram characteristics of size, position of thecentromere and sometimes the presence of achromosomal satellite (a segment distal to asecondary constriction), the human chromosomes are classified into the following groups:[15]
Very small, acrocentric (and 21, 22 withsatellite)
Alternatively, the human genome can be classified as follows, based on pairing, sex differences, as well as location within thecell nucleus versus insidemitochondria:
22 homologousautosomal chromosome pairs (chromosomes 1 to 22).Homologous means that they have the same genes in the same loci, and autosomal means that they are not sex chromomes.
Twosex chromosome (in green rectangle at bottom right in the schematic karyogram, with adjacent silhouettes of typical representativephenotypes): The most common karyotypes forfemales contain twoX chromosomes and are denoted 46,XX;males usually have both an X and aY chromosome denoted 46,XY. However, approximately 0.018% percent of humans areintersex, sometimes due to variations in sex chromosomes.[16]
Thehuman mitochondrial genome (shown at bottom left in the schematic karyogram, to scale compared to the nuclear DNA in terms ofbase pairs), although this is not included in micrographic karyograms in clinical practice. Its genome is relatively tiny compared to the rest.
Schematic karyograms generally display a DNA copy number corresponding to theG0 phase of the cellular state (outside of the replicativecell cycle) which is the most common state of cells. The schematic karyogram in this section also shows this state. In this state (as well as during the G1 phase of thecell cycle), each cell has two autosomal chromosomes of each kind (designated 2n), where each chromosome has one copy of eachlocus, making a total copy number of two for each locus (2c). At top center in the schematic karyogram, it also shows the chromosome 3 pair after having undergoneDNA synthesis, occurring in theS phase (annotated as S) of the cell cycle. This interval includes theG2 phase andmetaphase (annotated as "Meta."). During this interval, there is still 2n, but each chromosome will have two copies of each locus, wherein eachsister chromatid (chromosome arm) is connected at the centromere, for a total of 4c.[17] The chromosomes on micrographic karyograms are in this state as well, because they are generally micrographed in metaphase, but during this phase the two copies of each chromosome are so close to each other that they appear as one unless the image resolution is high enough to distinguish them. In reality, during the G0 and G1 phases, nuclear DNA is dispersed aschromatin and does not show visually distinguishable chromosomes even on micrography.
The copy number of thehuman mitochondrial genome per human cell varies from 0 (erythrocytes)[18] up to 1,500,000 (oocytes), mainly depending on the number of mitochondria per cell.[19]
Although thereplication andtranscription ofDNA is highly standardized ineukaryotes, the same cannot be said for their karyotypes, which are highly variable. There is variation between species in chromosome number, and in detailed organization, despite their construction from the samemacromolecules. This variation provides the basis for a range of studies in evolutionarycytology.
In some cases there is even significant variation within species. In a review, Godfrey and Masters conclude:
In our view, it is unlikely that one process or the other can independently account for the wide range of karyotype structures that are observed ... But, used in conjunction with other phylogenetic data, karyotypic fissioning may help to explain dramatic differences in diploid numbers between closely related species, which were previously inexplicable.[20]
Although much is known about karyotypes at the descriptive level, and it is clear that changes in karyotype organization has had effects on the evolutionary course of many species, it is quite unclear what the general significance might be.
We have a very poor understanding of the causes of karyotype evolution, despite many careful investigations ... the general significance of karyotype evolution is obscure.
Instead of the usual gene repression, some organisms go in for large-scale elimination ofheterochromatin, or other kinds of visible adjustment to the karyotype.
Chromosome elimination. In some species, as in manysciarid flies, entire chromosomes are eliminated during development.[22]
Chromatin diminution (founding father:Theodor Boveri). In this process, found in somecopepods androundworms such asAscaris suum, portions of the chromosomes are cast away in particular cells. This process is a carefully organised genome rearrangement where new telomeres are constructed and certain heterochromatin regions are lost.[23][24] InA. suum, all the somatic cell precursors undergo chromatin diminution.[25]
X-inactivation. The inactivation of one X chromosome takes place during the early development of mammals (seeBarr body anddosage compensation). Inplacental mammals, the inactivation is random as between the two Xs; thus the mammalian female is a mosaic in respect of her X chromosomes. Inmarsupials it is always the paternal X which is inactivated. In human females some 15% of somatic cells escape inactivation,[26] and the number of genes affected on the inactivated X chromosome varies between cells: infibroblast cells up about 25% of genes on the Barr body escape inactivation.[27]
A spectacular example of variability between closely related species is themuntjac, which was investigated byKurt Benirschke andDoris Wurster. The diploid number of the Chinese muntjac,Muntiacus reevesi, was found to be 46, alltelocentric. When they looked at the karyotype of the closely related Indian muntjac,Muntiacus muntjak, they were astonished to find it had female = 6, male = 7 chromosomes.[28]
They simply could not believe what they saw ... They kept quiet for two or three years because they thought something was wrong with their tissue culture ... But when they obtained a couple more specimens they confirmed [their findings].
The number of chromosomes in the karyotype between (relatively) unrelated species is hugely variable. The low record is held by thenematodeParascaris univalens, where thehaploid n = 1; and an ant:Myrmecia pilosula.[30] The high record would be somewhere amongst theferns, with the adder's tongue fernOphioglossum ahead with an average of 1262 chromosomes.[31] Top score for animals might be theshortnose sturgeonAcipenser brevirostrum at 372 chromosomes.[32] The existence of supernumerary orB chromosomes means that chromosome number can vary even within one interbreeding population; andaneuploids are another example, though in this case they would not be regarded as normal members of the population.
The fundamental number,FN, of a karyotype is the number of visible major chromosomal arms per set of chromosomes.[33][34] Thus, FN ≤ 2 × 2n, the difference depending on the number of chromosomes considered single-armed (acrocentric ortelocentric) present. Humans have FN = 82,[35] due to the presence of five acrocentric chromosome pairs:13,14,15,21, and22 (the humanY chromosome is also acrocentric). The fundamental autosomal number or autosomal fundamental number,FNa[36] orAN,[37] of a karyotype is the number of visible major chromosomal arms per set ofautosomes (non-sex-linked chromosomes).
For the investigation of ancient karyotype duplications, seePaleopolyploidy.
Ploidy is the number of complete sets of chromosomes in a cell.
Polyploidy, where there are more than two sets of homologous chromosomes in the cells, occurs mainly in plants. It has been of major significance in plant evolution according toStebbins.[38][39][40][41] The proportion of flowering plants which are polyploid was estimated by Stebbins to be 30–35%, but in grasses the average is much higher, about 70%.[42] Polyploidy in lower plants (ferns,horsetails andpsilotales) is also common, and some species of ferns have reached levels of polyploidy far in excess of the highest levels known in flowering plants. Polyploidy in animals is much less common, but it has been significant in some groups.[43]
Polyploid series in related species which consist entirely of multiples of a single basic number are known aseuploid.
In many instances, endopolyploid nuclei contain tens of thousands of chromosomes (which cannot be exactly counted). The cells do not always contain exact multiples (powers of two), which is why the simple definition 'an increase in the number of chromosome sets caused by replication without cell division' is not quite accurate.
This process (especially studied in insects and some higher plants such as maize) may be a developmental strategy for increasing the productivity of tissues which are highly active in biosynthesis.[46]
Aneuploidy is the condition in which the chromosome number in the cells is not the typical number for the species. This would give rise to achromosome abnormality such as an extra chromosome or one or more chromosomes lost. Abnormalities in chromosome number usually cause a defect in development.Down syndrome andTurner syndrome are examples of this.
Aneuploidy may also occur within a group of closely related species. Classic examples in plants are the genusCrepis, where the gametic (= haploid) numbers form the series x = 3, 4, 5, 6, and 7; andCrocus, where every number from x = 3 to x = 15 is represented by at least one species. Evidence of various kinds shows that trends of evolution have gone in different directions in different groups.[48] In primates, thegreat apes have 24x2 chromosomes whereas humans have 23x2.Human chromosome 2 was formed by a merger of ancestral chromosomes, reducing the number.[49]
Some species arepolymorphic for different chromosome structural forms.[50] The structural variation may be associated with different numbers of chromosomes in different individuals, which occurs in the ladybird beetleChilocorus stigma, somemantids of the genusAmeles,[51] the European shrewSorex araneus.[52] There is some evidence from the case of themolluscThais lapillus (thedog whelk) on theBrittany coast, that the two chromosome morphs areadapted to different habitats.[53]
The detailed study of chromosome banding in insects withpolytene chromosomes can reveal relationships between closely related species: the classic example is the study of chromosome banding inHawaiian drosophilids byHampton L. Carson.
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, especiallyinversions, 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. UsingK-Ar dating, the present islands date from 0.4 million years ago (mya) (Mauna Kea) to 10mya (Necker). The oldest member of the Hawaiian archipelago still above the sea isKure Atoll, which can be dated to 30 mya. The archipelago itself (produced by thePacific Plate moving over ahot spot) has existed for far longer, at least into theCretaceous. Previous islands now beneath the sea (guyots) form theEmperor Seamount Chain.[54]
All of the nativeDrosophila andScaptomyza species in Hawaiʻi have apparently descended from a single ancestral species that colonized the islands, probably 20 million years ago. The subsequentadaptive radiation was spurred by a lack ofcompetition and a wide variety ofniches. Although it would be possible for a singlegravid female to colonise an island, it is more likely to have been a group from the same species.[55][56][57][58]
There are other animals and plants on the Hawaiian archipelago which have undergone similar, if less spectacular, adaptive radiations.[59][60]
Chromosomes display a banded pattern when treated with some stains. Bands are alternating light and dark stripes that appear along the lengths of chromosomes. Unique banding patterns are used to identify chromosomes and to diagnose chromosomal aberrations, including chromosome breakage, loss, duplication, translocation or inverted segments. A range of different chromosome treatments produce a range of banding patterns: G-bands, R-bands, C-bands, Q-bands, T-bands and NOR-bands.
Cytogenetics employs several techniques to visualize different aspects of chromosomes:[9]
G-banding is obtained withGiemsa stain following digestion of chromosomes withtrypsin. 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. It is the most common chromosome banding method.[61]
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 toconstitutive heterochromatin, so it stainscentromeres. The name is derived from centromeric or constitutive heterochromatin. The preparations undergo alkaline denaturation prior to staining leading to an almost complete depurination of the DNA. After washing the probe the remaining DNA is renatured again and stained with Giemsa solution consisting of methylene azure, methylene violet, methylene blue, and eosin. Heterochromatin binds a lot of the dye, while the rest of the chromosomes absorb only little of it. The C-bonding proved to be especially well-suited for the characterization of plant chromosomes.
Q-banding is afluorescent pattern obtained usingquinacrine for staining. The pattern of bands is very similar to that seen in G-banding. They can be recognized by a yellow fluorescence of differing intensity. Most part of the stained DNA is heterochromatin. Quinacrin (atebrin) binds both regions rich in AT and in GC, but only the AT-quinacrin-complex fluoresces. Since regions rich in AT are more common in heterochromatin than in euchromatin, these regions are labelled preferentially. The different intensities of the single bands mirror the different contents of AT. Other fluorochromes like DAPI or Hoechst 33258 lead also to characteristic, reproducible patterns. Each of them produces its specific pattern. In other words: the properties of the bonds and the specificity of the fluorochromes are not exclusively based on their affinity to regions rich in AT. Rather, the distribution of AT and the association of AT with other molecules like histones, for example, influences the binding properties of the fluorochromes.
Silver staining:Silver nitrate stains thenucleolar organization region-associated protein. This yields a dark region where the silver is deposited, denoting the activity of rRNA genes within the NOR.
In the "classic" (depicted) karyotype, adye, oftenGiemsa(G-banding), less frequentlymepacrine (quinacrine), is used to stain bands on the chromosomes. Giemsa is specific for thephosphate groups ofDNA. Quinacrine binds to theadenine-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 armsp andq, respectively. In addition, the differently stained regions and sub-regions are given numerical designations fromproximal todistal 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 p15.2 (thelocus on the chromosome), which is written as 46,XX,del(5)(p15.2).[62]
Multicolor FISH (mFISH) and spectral karyotype (SKY technique)
MulticolorFISH and the older spectral karyotyping are molecularcytogenetic techniques used to simultaneously visualize all the pairs ofchromosomes in an organism in different colors.Fluorescently labeled probes for each chromosome are made by labeling chromosome-specific DNA with differentfluorophores. Because there are a limited number of spectrally distinct fluorophores, a combinatorial labeling method is used to generate many different colors. Fluorophore combinations are captured and analyzed by a fluorescence microscope using up to 7 narrow-banded fluorescence filters or, in the case of spectral karyotyping, by using aninterferometer attached to a fluorescence microscope. In the case of an mFISH image, every combination of fluorochromes from the resulting original images is replaced by apseudo color in a dedicated image analysis software. Thus, chromosomes or chromosome sections can be visualized and identified, allowing for the analysis of chromosomal rearrangements.[63]In the case of spectral karyotyping, image processing software assigns apseudo color to each spectrally different combination, allowing the visualization of the individually colored chromosomes.[64]
Spectral human karyotype
Multicolor FISH is used to identify structural chromosome aberrations in cancer cells and other disease conditions when Giemsa banding or other techniques are not accurate enough.
Digital karyotyping is a technique used to quantify the DNA copy number on a genomic scale. Short sequences of DNA from specific loci all over the genome are isolated and enumerated.[65] This method is also known asvirtual karyotyping. Using this technique, it is possible to detect small alterations in the human genome, that cannot be detected through methods employing metaphase chromosomes. Some loci deletions are known to be related to the development of cancer. Such deletions are found through digital karyotyping using the loci associated with cancer development.[66]
Chromosome abnormalities can be numerical, as in the presence of extra or missing chromosomes, or structural, as inderivative chromosome,translocations,inversions, large-scale deletions or duplications. Numerical abnormalities, also known asaneuploidy, often occur as a result ofnondisjunction duringmeiosis in the formation of agamete;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 inhomologous 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 duringmitosis and give rise to agenetic mosaic individual who has some normal and some abnormal cells.
Trisomy 9, believed to be the 4th most common trisomy, has many long lived affected individuals but only in a form other than a full trisomy, such as trisomy 9p syndrome or mosaic trisomy 9. They often function quite well, but tend to have trouble with speech.
Also documented are trisomy 8 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.
Angelman syndrome – 50% of cases have a segment of the long arm of chromosome 15 missing; a deletion of the maternal genes, example ofimprinting disorder.
Prader-Willi syndrome – 50% of cases have a segment of the long arm of chromosome 15 missing; a deletion of the paternal genes, example of imprinting disorder.
The next stage took place after the development of genetics in the early 20th century, when it was appreciated that chromosomes (that can be observed by karyotype) were the carrier of genes. The term karyotype as defined by thephenotypic appearance of thesomatic chromosomes, in contrast to theirgenic contents was introduced byGrigory Levitsky who worked with Lev Delaunay,Sergei Navashin, andNikolai Vavilov.[67][68][69][70] The subsequent history of the concept can be followed in the works ofC. D. Darlington[71] andMichael JD White.[4][13]
Investigation into the human karyotype took many years to settle the most basic question: how many chromosomes does a normaldiploid human cell contain?[72] In 1912,Hans von Winiwarter reported 47 chromosomes inspermatogonia and 48 inoogonia, concluding anXX/XO sex determination mechanism.[73]Painter in 1922 was not certain whether the diploid of humans was 46 or 48, at first favoring 46,[74] but revised his opinion from 46 to 48, and he correctly insisted on humans having anXX/XY system.[75] Considering the techniques of the time, these results were remarkable.
Fusion of ancestral chromosomes left distinctive remnants of telomeres, and a vestigial centromere
Joe Hin Tjio working inAlbert Levan's lab[76] found the chromosome count to be 46 using new techniques available at the time:
Squashing the preparation on the slide forcing the chromosomes into a single plane
Cutting up a photomicrograph and arranging the result into an indisputable karyogram.
The work took place in 1955, and was published in 1956. The karyotype of humans includes only 46 chromosomes.[77][29] The othergreat apes have 48 chromosomes.Human chromosome 2 is now known to be a result of an end-to-end fusion of two ancestral ape chromosomes.[78][79]
^Judd, Walter S.; Campbell, Christopher S.; Kellogg, Elizabeth A.; Stevens, Peter F.; Donoghue, Michael J. (2002).Plant systematics, a phylogenetic approach (2 ed.). Sunderland MA, US: Sinauer Associates Inc. p. 544.ISBN0-87893-403-0.
^King, R.C.; Stansfield, W.D.; Mulligan, P.K. (2006).A dictionary of genetics (7th ed.). Oxford University Press. p. 242.
^Shuster RC, Rubenstein AJ, Wallace DC (1988). "Mitochondrial DNA in anucleate human blood cells".Biochem Biophys Res Commun.155 (3):1360–5.doi:10.1016/s0006-291x(88)81291-9.PMID3178814.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Khandelwal S. (1990). "Chromosome evolution in the genus Ophioglossum L".Botanical Journal of the Linnean Society.102 (3):205–217.doi:10.1111/j.1095-8339.1990.tb01876.x.
^Kim, D.S.; Nam, Y.K.; Noh, J.K.; Park, C.H.; Chapman, F.A. (2005). "Karyotype of North American shortnose sturgeonAcipenser brevirostrum with the highest chromosome number in the Acipenseriformes".Ichthyological Research.52 (1):94–97.Bibcode:2005IchtR..52...94K.doi:10.1007/s10228-004-0257-z.S2CID20126376.
^Matthey, R. (15 May 1945). "L'evolution de la formule chromosomiale chez les vertébrés".Experientia (Basel).1 (2):50–56.doi:10.1007/BF02153623.S2CID38524594.
^Nagl, W. (1978).Endopolyploidy and polyteny in differentiation and evolution: towards an understanding of quantitative and qualitative variation of nuclear DNA in ontogeny and phylogeny. New York: Elsevier.
^Stebbins, G. Ledley, Jr. 1972.Chromosomal evolution in higher plants. Nelson, London. p18
^Searle, J. B. (1 June 1984). "Three New Karyotypic Races of the Common Shrew Sorex Araneus (Mammalia: Insectivora) and a Phylogeny".Systematic Biology.33 (2):184–194.doi:10.1093/sysbio/33.2.184.ISSN1063-5157.
^Clague, D.A.; Dalrymple, G.B. (1987)."The Hawaiian-Emperor volcanic chain, Part I. Geologic evolution"(PDF). In Decker, R.W.; Wright, T.L.; Stauffer, P.H. (eds.).Volcanism in Hawaii. Vol. 1. pp. 5–54. U.S. Geological Survey Professional Paper 1350. Archived fromthe original(PDF) on 10 October 2012. Retrieved28 May 2013.
^Craddock E.M. (2000). "Speciation Processes in the Adaptive Radiation of Hawaiian Plants and Animals". In Hecht, Max K.; MacIntyre, Ross J.; Clegg, Michael T. (eds.).Evolutionary Biology. Vol. 31. pp. 1–43.doi:10.1007/978-1-4615-4185-1_1.ISBN978-1-4613-6877-9.
^Maloy, Stanley R.; Hughes, Kelly (2013).Brenner's Encyclopedia of Genetics. San Diego, CA: Academic Press.ISBN978-0-08-096156-9.OCLC836404630.
^Lisa G. Shaffer; Niels Tommerup, eds. (2005).ISCN 2005: An International System for Human Cytogenetic Nomenclature. Switzerland: S. Karger AG.ISBN978-3-8055-8019-9.
^Liehr T, Starke H, Weise A, Lehrer H, Claussen U (January 2004). "Multicolour FISH probe sets and their applications".Histol. Histopathol.19 (1):229–237.PMID14702191.
^Delaunay L. N.Comparative karyological study of species Muscari Mill. and Bellevalia Lapeyr. Bulletin of the Tiflis Botanical Garden. 1922, v. 2, n. 1, p. 1-32[in Russian]
^Darlington C.D. 1939.Evolution of genetic systems. Cambridge University Press. 2nd ed, revised and enlarged, 1958. Oliver & Boyd, Edinburgh.
^MJ, Kottler (1974). "From 48 to 46: cytological technique, preconception, and the counting of human chromosomes".Bull Hist Med.48 (4):465–502.PMID4618149.
^von Winiwarter H. (1912). "Études sur la spermatogenèse humaine".Archives de Biologie.27 (93):147–9.
^Painter T.S. (1922). "The spermatogenesis of man".Anat. Res.23: 129.
^Painter T.S. (1923). "Studies in mammalian spermatogenesis II".J. Exp. Zoology.37 (3):291–336.doi:10.1002/jez.1400370303.
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