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Aneuploidy & chromosomal rearrangements

Aneuploidy and nondisjunction. Down syndrome and related disorders. Chromosomal rearrangements.


Some things just work well in pairs. Everyday examples include shoes, gloves, and the earbuds on a music player. If you're missing one member of a pair, it's likely to be a nuisance, and might even be a serious problem (for instance, if you're already late for school!).
Pairs are important in genetics, too. Most of your cells contain 46 chromosomes, rod-like structures made of DNA and protein, that come in 23 matched pairs. These chromosomes carry tens of thousands of genes, which tell your body how to develop and which keep it functioning from moment to moment during your lifetime1.
Image credit: "Human genome," by Webridge (CC BY 2.0).
If a chromosome pair loses or gains a member, or even part of a member, the delicate balance of the human body may be disrupted. In this article, we’ll examine how changes in chromosome number and structure come about, and how they can affect human health.

Aneuploidy: Extra or missing chromosomes

Changes in a cell's genetic material are called mutations. In one form of mutation, cells may end up with an extra or missing chromosome.
Each species has a characteristic chromosome number, such as 46 chromosomes for a typical human body cell. In organisms with two full chromosomes sets, such as humans, this number is given the name 2n. When an organism or cell contains 2n chromosomes (or some other multiple of n), it is said to be euploid, meaning that it contains chromosomes correctly organized into complete sets (eu- = good).
If a cell is missing one or more chromosomes, it is said to be aneuploid (an- = not, "not good"). For instance, human somatic cells with chromosome numbers of (2n1)=45 or (2n+1)=47 are aneuploid. Similarly, a normal human egg or sperm has just one set of chromosomes (n=23). An egg or sperm with (n1)=22 or (n+1)=24 chromosomes is considered to be aneuploid.
Two common types of aneuploidy have their own special names:
  • Monosomy is when an organism has only one copy of a chromosome that should be present in two copies (2n1).
  • Trisomy is when an organism has a third copy of a chromosome that should be present in two copies (2n+1).
Image modified from "NHGRI human male karyotype," by the National Human Genome Research Institute (public domain).
Aneuploidy also includes cases where a cell has larger numbers of extra or missing chromosomes, as in (2n2),(2n+3), etc. However, if there is an entire extra or missing chromosome set (e.g., 3n), this is not formally considered to be aneuploidy, even though it may still be bad for the cell or organism. Organisms with more than two complete sets of chromosomes are said to be polyploid.

Nondisjunction of chromosomes

Disorders of chromosome number are caused by nondisjunction, which occurs when pairs of homologous chromosomes or sister chromatids fail to separate during meiosis I or II (or during mitosis).
Meiosis I. The diagram below shows how nondisjunction can take place during meiosis I if homologous chromosomes don't separate, and how this can lead to the production of aneuploid gametes (eggs or sperm):
Meiosis II. Nondisjunction can also happen in meiosis II, with sister chromatids (instead of homologous chromosomes) failing to separate. Again, some gametes contain extra or missing chromosomes:
Mitosis. Nondisjunction can also happen during mitosis. In humans, chromosome changes due to nondisjunction during mitosis in body cells will not be passed on to children (because these cells don't make sperm and eggs). But mitotic nondisjunction can cause other problems: cancer cells often have abnormal chromosome numbers2.
When an aneuploid sperm or egg combines with a normal sperm or egg in fertilization, it makes a zygote that is also aneuploid. For instance, if a sperm cell with one extra chromosome (n+1) combines with a normal egg cell (n), the resulting zygote, or one-celled embryo, will have a chromosome number of 2n+1.

Genetic disorders caused by aneuploidy

Human embryos that are missing a copy of any autosome (non-sex chromosome) fail to develop to birth. In other words, human autosomal monosomies are always lethal. That's because the embryos have too low a "dosage" of the proteins and other gene products that are encoded by genes on the missing chromosome3.
Most autosomal trisomies also prevent an embryo from developing to birth. However, an extra copy of some of the smaller chromosomes (13, 15, 18, 21, or 22) can allow the affected individual to survive for a short period past birth, or, in some cases, for many years. When an extra chromosome is present, it can cause problems in development due to an imbalance between the gene products from the duplicated chromosome and those from other chromosomes3.
The most common trisomy among embryos that survive to birth is Down syndrome, or trisomy 21. People with this inherited disorder have short stature and digits, facial distinctions including a broad skull and large tongue, and developmental delays. Here is a karyotype, or image of the chromosomes, from a person with Down syndrome, showing the characteristic three copies of chromosome 21:
Image credit: "21 trisomy - Down syndrome," by the U.S. Department of Energy Human Genome Program (public domain).
About 1 in every 800 newborns is born with Down syndrome4. However, the likelihood that a pregnancy will result in an embryo with Down syndrome goes up with a woman's age, particularly above 40 years5,6. This is probably because of more frequent nondisjunction in the developing eggs of older women.
Human genetic disorders can also be caused by aneuploidies involving sex chromosomes. These aneuploidies are better-tolerated than autosomal ones because human cells have the ability to shut down extra X chromosomes in a process called X-inactivation. You can learn more in the article on X chromosome inactivation.

Chromosomal rearrangements

In another class of large-scale mutations, big chunks of chromosomes (but not entire chromosomes) are affected. Such changes are called chromosomal rearrangements. They include:
  • A duplication, where part of a chromosome is copied.
  • A deletion, where part of a chromosome is removed.
  • An inversion, where chromosomal region is flipped around so that it points in the opposite direction.
    Image modified from "Chromosomenmutation," by Deitzel66, modified from NIH Talking Glossary of Genetics (public domain).
  • A translocation, where a piece of one chromosome gets attached to another chromosome. A reciprocal translocation involves two chromosomes swapping segments; a non-reciprocal translocation means that a chunk of one chromosome moves to another.
    Image modified from "Chromosomenmutation," by Deitzel66, modified from NIH Talking Glossary of Genetics (public domain).
In some cases, a chromosomal rearrangement causes symptoms similar to the loss or gain of an entire chromosome. For instance, Down syndrome is usually caused by a third copy of chromosome 21, but it can also occur when a large piece of chromosome 21 moves to another chromosome (and is passed on to offspring along with a regular chromosome 21)4. In other cases, rearrangements cause unique disorders, ones that are not associated with aneuploidy.

Want to join the conversation?

  • duskpin tree style avatar for user Camila Rodrigues
    And what about a cell/organism containing 2n - 2 chromosomes, supposing these two missing ones are paired up? Is this cell/organism considered aneuploid or euploid?
    (10 votes)
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  • piceratops tree style avatar for user Mike Grey
    How is chromosomal "rearrangement" different from "crossover"?
    (12 votes)
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    • leaf green style avatar for user jailynn.harke
      Crossovers (recombination events) occur between homologous chromosomes (actually sister chromatids). Meaning, recombination occurs between chr13 sister chromatid from Mom crossing over with sister chromatid of chr13 from Dad.
      Duplications and inversions can happen on a single chromosome. So, you can have a region of, let’s say, chr22 duplicated. Or that region might get inverted. Translocations can involve a region of (for example) chr13 swapping places with a region of chr22.
      I think the key is that crossovers are typically between homologous chromosomes whereas rearrangements are a broader category where they CAN be between homologs but there are also non-homologous chromosomal rearrangements.
      (15 votes)
  • blobby green style avatar for user Ethan Jandrew
    If there was an instance of a gamete with -1 chromosome and a gamete with +1 chromosome that joined together, would that individual be considered "normal"?
    (5 votes)
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  • blobby green style avatar for user Taylor
    If there's a diploid (2n) cell that went through the cell cycle but somehow all of the chromosomes stuck together and went to one daughter cell while the other daughter cell had no chromosomes, is the daughter cell with the chromosomes considered tetraploid (4n) at that point because there are now 4 chromosomes per homologous pair, or would it actually be considered 2n+2n? For instance, if n=12, then it would be 2n+24?
    (4 votes)
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    • aqualine seed style avatar for user Anita Câp'n-Swâggette
      The likelihood of that actually happening is very rare. But that does not mean it's impossible, there's never a 0% (or 100%) of anything in science (in most cases).
      If that was to happen it would be called tetraploid a form of polyploidy. It's not likely to happen but it has happened a species of frogs (from the genus Neobatrachus) has been found where they actually contain 4n instead of the usual 2n. The probability of one of these mutations to occur is low, and then to have this happen [at least] twice and to find each other to mate was probably close to 0%.
      (4 votes)
  • duskpin ultimate style avatar for user RiverclanWarrior
    What are examples of trisomies that allow the offspring to survive other than Down Syndrome?
    (4 votes)
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  • blobby green style avatar for user sbrown103
    does nondisjunction automatically lead to one monosomy and one trisomy?
    (4 votes)
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    • winston baby style avatar for user Ivana - Science trainee
      Mitotic nondisjunction can occur with the inactivation of either topoisomerase II, condensin, or separate. This will result in 2 diploid daughter cells, one with 2n+1 and the other with 2n-1.

      If nondisjunction occurs during meiosis I, it is the result of the failure of the tetrads to separate during anaphase I. At the end of meiosis I, there will be 2 haploid daughter cells, one with n+1 and the other with n-1. Both of these daughter cells will then go on to divide once more in meiosis 2, producing 4 daughter cells, 2 with n+1 and 2 with n-1.

      Nondisjunction in meiosis II results from the failure of the sister chromatids to separate during anaphase II. Since meiosis I proceeded without error, 2 of the 4 daughter cells will have the normal haploid number. The other 2 daughter cells will be aneuploid, one with n+1 and the other with n-1.

      If meiotic nondisjunction, then yes. The result is monosomy and trisomy.

      (2 votes)
  • aqualine seed style avatar for user John Nardella
    Curious to know if there is any evolutionary effect on how human (and other eukaryotic organisms) chromosomes are ordered. For example, is there something evolutionarily special or significant about the genes encoded on chromosome 1 versus the genes encoded on chromosome 22?
    (4 votes)
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  • blobby green style avatar for user Clifford
    what would happen if a 2n-1 and 2n+1 gamete combined?
    (4 votes)
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  • purple pi teal style avatar for user Viraj Zaveri
    Is translocation essentially formed from the process of crossing over?
    (3 votes)
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    • female robot grace style avatar for user tyersome
      Good question!

      Translocations can be the result of crossing over between sequences that are similar but located on different chromosomes.

      One source of these events are the repetitive elements§ that make up most of the genome in many species including humans.

      Another way that translocations can happen is if the DNA is broken in multiple places — e.g. by exposure to radiation.
      In some cases the DNA will heal, but with the "wrong" parts of chromosomes stuck together.

      §Note: A major component of the repetitive DNA comes from the many different families of transposons — pieces of DNA that can copy themselves to new places within the genome.
      (2 votes)
  • piceratops tree style avatar for user Z.ZeNgYntoN
    Is the annotation of the daughter cells for the nonjunction in mitosis diagram wrong? I think the upper one is 2n-1 and the bottom one is 2n+1
    (3 votes)
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