How does nondisjunction cause chromosome number disorders

For instance, fertilization of an abnormal diploid egg with a normal haploid sperm would yield a triploid zygote. Polyploid animals are extremely rare, with only a few examples among the flatworms, crustaceans, amphibians, fish, and lizards. Triploid animals are sterile because meiosis cannot proceed normally with an odd number of chromosome sets. In contrast, polyploidy is very common in the plant kingdom, and polyploid plants tend to be larger and more robust than euploids of their species.

Cytologists have characterized numerous structural rearrangements in chromosomes, including partial duplications, deletions, inversions, and translocations. Duplications and deletions often produce offspring that survive but exhibit physical and mental abnormalities. Chromosome inversions and translocations can be identified by observing cells during meiosis because homologous chromosomes with a rearrangement in one of the pair must contort to maintain appropriate gene alignment and pair effectively during prophase I.

Unless they disrupt a gene sequence, inversions only change the orientation of genes and are likely to have more mild effects than aneuploid errors. The Chromosome 18 InversionNot all structural rearrangements of chromosomes produce nonviable, impaired, or infertile individuals.

In rare instances, such a change can result in the evolution of a new species. In fact, an inversion in chromosome 18 appears to have contributed to the evolution of humans. This inversion is not present in our closest genetic relatives, the chimpanzees. The chromosome 18 inversion is believed to have occurred in early humans following their divergence from a common ancestor with chimpanzees approximately five million years ago.

Researchers have suggested that a long stretch of DNA was duplicated on chromosome 18 of an ancestor to humans, but that during the duplication it was inverted inserted into the chromosome in reverse orientation. A comparison of human and chimpanzee genes in the region of this inversion indicates that two genes— ROCK1 and USP14 —are farther apart on human chromosome 18 than they are on the corresponding chimpanzee chromosome.

This suggests that one of the inversion breakpoints occurred between these two genes. Interestingly, humans and chimpanzees express USP14 at distinct levels in specific cell types, including cortical cells and fibroblasts.

Perhaps the chromosome 18 inversion in an ancestral human repositioned specific genes and reset their expression levels in a useful way. It is not known how this inversion contributed to hominid evolution, but it appears to be a significant factor in the divergence of humans from other primates.

A translocation occurs when a segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome. Translocations can be benign or have devastating effects, depending on how the positions of genes are altered with respect to regulatory sequences.

Notably, specific translocations have been associated with several cancers and with schizophrenia. Reciprocal translocations result from the exchange of chromosome segments between two nonhomologous chromosomes such that there is no gain or loss of genetic information Figure 7.

Individuals with Turner's syndrome XO are females with a single X chromosome. They are sterile, possess underdeveloped secondary sexual characteristics and they are shorter than normal. This condition occurs in about 1 in female's births worldwide Females with genetic constitution XXX, on the other hand, have a normal appearance and are fertile, but suffer from a mild mental handicap. Similarly, XYY males have relatively few clinical symptoms and appear phenotypically normal.

They are taller than average and may show aggressive behavior and below-average intelligence. The analysis and interpretation of these results can bold the principal causes of non-disjunction such as, the maternal age, as it elevates the risk of nondisjunction 8 , meiotic errors in both phases I and II which was demonstrated in many studies Thus the chromosomal nondisjunction doesn't have a unique cause, it is the result of meiotic errors of paternal and maternal origin and many other factors such maternal age, translocations and exposure to toxic substances.

There are differences in the frequencies and percentages of the errors incidence as shown throughout the review Nowadays we consider that we have finished the easy part, but still have to search for the difficult one, which is the treatment, prevention and avoiding the occurrence of these abnormalities, so will it be possible? Benjamin L. York: Oxford University Press.

Len L, MD. Published Strachan, Tom, and Andrew P. Human Molecular Genetics. Oxford: U. Nelson J, Ramirez et al. Parental origin, nondisjunction, and recombination of the extra chromosome 21 in Down syndrome: a study in a sample of the Colombian population. Application of quantitative fluorescent PCR with short tandem repeat markers to the study of aneuploidies in spontaneous miscarriages. Hum Reprod ; Petersen M, Mikkelsen M.

Nondisjunction in trisomy origin and mechanisms. Cytogenet Cell Genet ; Elucidating the mechanisms of paternal non-disjunction of chromosome 21 in humans. Hum Mol Genet ; Brandt, Mads Bak, Claus H. Non-disjunction of chromosome Published by Oxford University Press; Reduced recombination in maternal meiosis coupled with non-disjunction at meiosis II leading to recurrent 47, XXX.

Chromosome Research ; - Facts about Down syndrome. Published on 15 august Oxford University Press; Hallare A, Gervasio M. Monitoring genotoxicity among gasoline station attendants and traffic enforcers in the City of Manila using the micronucleus assay with exfoliated epithelial cells.

Analysis of meiotic segregation patterns and interchromosomal effects in sperm from six males with Robertsonian translocations. Alberts, Bruce, et al. Molecular Biology of the Cell. New York: Garland Publishing; [ Links ] Genet Effect of meiotic recombination on the production of aneuploid gametes in humans. Genome Res. Lamb N, Shaffer J. Association between maternal age and meiotic recombination for trisomy Relationship of recombination patterns and maternal age among non-disjoined chromosomes Trans ; - Variation in MLH1 distribution in recombination maps for individual chromosomes from human males.

Genet ; - Synaptic defects at meiosis I and non-obstructive azoospermia. Reprod ; Immunofluorescent synaptonemal complex analysis in azoospermic men. Genome Res ; - Abnormal progression through meiosis in men with nonobstructive azoospermia. Steril ; - Martin R. Meiotic chromosome abnormalities in human spermatogenesis. Toxicol ; - Extreme heterogeneity in the molecular events leading to the establishment of chiasmata during meiosis I in human oocytes.

Online ; - Near-human aneuploidy levels in female mice with homeologous chromosomes. Biol ; - Roy A, Matzuk M. Deconstructing mammalian reproduction: using knockouts to define fertility pathways. Reproduction ; - Cooke H. SYCE2 is required for synaptonemal complex assembly, double strand break repair, and homologous recombination. Cell Biol ; A comparison of human and chimpanzee genes in the region of this inversion indicates that two genes—ROCK1 and USP14—that are adjacent on chimpanzee chromosome 17 which corresponds to human chromosome 18 are more distantly positioned on human chromosome This suggests that one of the inversion breakpoints occurred between these two genes.

Interestingly, humans and chimpanzees express USP14 at distinct levels in specific cell types, including cortical cells and fibroblasts. Perhaps the chromosome 18 inversion in an ancestral human repositioned specific genes and reset their expression levels in a useful way. It is not known how this inversion contributed to hominid evolution, but it appears to be a significant factor in the divergence of humans from other primates.

A translocation occurs when a segment of a chromosome dissociates and reattaches to a different, nonhomologous chromosome. Translocations can be benign or have devastating effects depending on how the positions of genes are altered with respect to regulatory sequences. Notably, specific translocations have been associated with several cancers and with schizophrenia. Reciprocal translocations result from the exchange of chromosome segments between two nonhomologous chromosomes such that there is no gain or loss of genetic information.

Reciprocal translocations do not involve loss of genetic information : A reciprocal translocation occurs when a segment of DNA is transferred from one chromosome to another, nonhomologous chromosome. The presence of extra X chromosomes in a cell is compensated for by X-inactivation in which all but one X chromosome are silenced. Humans display dramatic deleterious effects with autosomal trisomies and monosomies. Therefore, it may seem counterintuitive that human females and males can function normally, despite carrying different numbers of the X chromosome.

Rather than a gain or loss of autosomes, variations in the number of X chromosomes are associated with relatively mild effects. In part, this occurs because of a molecular process called X inactivation. Early in development, when female mammalian embryos consist of just a few thousand cells relative to trillions in the newborn , one X chromosome in each cell inactivates by tightly condensing into a quiescent dormant structure called a Barr body.

The chance that an X chromosome maternally or paternally derived is inactivated in each cell is random, but once the inactivation occurs, all cells derived from that single cell will have the same inactive X chromosome or Barr body. By this process, a phenomenon called dosage compensation is achieved. Females possess two X chromosomes, while males have only one; therefore, if both X chromosomes remained active in the female, they would produce twice as much product from the genes on the X chromosomes as males.

So how does X-inactivation help alleviate the effects of extra X chromosomes? An individual carrying an abnormal number of X chromosomes will inactivate all but one X chromosome in each of her cells. If three X chromosomes are present, the cell will inactivate two of them. If four X chromosomes are present, three will be inactivated, and so on.

This results in an individual that is relatively phenotypically normal. However, even inactivated X chromosomes continue to express a few genes, and X chromosomes must reactivate for the proper maturation of female ovaries. As a result, X-chromosomal abnormalities are typically associated with mild mental and physical defects, as well as sterility. If the X chromosome is absent altogether, the individual will not develop in utero.

In contrast, polyploidy is very common in the plant kingdom, and polyploid plants tend to be larger and more robust than euploids of their species Figure 3.

Humans display dramatic deleterious effects with autosomal trisomies and monosomies. Therefore, it may seem counterintuitive that human females and males can function normally, despite carrying different numbers of the X chromosome. Rather than a gain or loss of autosomes, variations in the number of sex chromosomes are associated with relatively mild effects.

In part, this occurs because of a molecular process called X inactivation. Early in development, when female mammalian embryos consist of just a few thousand cells relative to trillions in the newborn , one X chromosome in each cell inactivates by tightly condensing into a quiescent dormant structure called a Barr body.

The chance that an X chromosome maternally or paternally derived is inactivated in each cell is random, but once the inactivation occurs, all cells derived from that one will have the same inactive X chromosome or Barr body. By this process, females compensate for their double genetic dose of X chromosome. Figure 4. In cats, the gene for coat color is located on the X chromosome. In the embryonic development of female cats, one of the two X chromosomes is randomly inactivated in each cell, resulting in a tortoiseshell pattern if the cat has two different alleles for coat color.

Male cats, having only one X chromosome, never exhibit a tortoiseshell coat color. Females that are heterozygous for an X-linked coat color gene will express one of two different coat colors over different regions of their body, corresponding to whichever X chromosome is inactivated in the embryonic cell progenitor of that region.

An individual carrying an abnormal number of X chromosomes will inactivate all but one X chromosome in each of her cells. However, even inactivated X chromosomes continue to express a few genes, and X chromosomes must reactivate for the proper maturation of female ovaries.

As a result, X-chromosomal abnormalities are typically associated with mild mental and physical defects, as well as sterility. If the X chromosome is absent altogether, the individual will not develop in utero.