Topic 7: Variations in Chromosome Number

A normal human (somatic) cell contains 46 chromosomes. This is because there are two sets of 23 chromosomes, one set from the mother and the other set from the father, known as the diploid state of 46 chromosomes. When a cell divides, the chromosomes replicate and the duplicates are distributed to each daughter cell; hence, each daughter cell has 46 chromosomes and is, from a genetic perspective, quantitatively and qualitatively identical to the parent cell. However, life is never perfect, so there are often variations on chromosome number. A polyploidy state is when whole sets of chromosomes are present in excess of the normal, or euploid. Another way in which chromosomes may vary in number is known aneuploidy. This is the gain or loss of individual chromosomes from the normal set of 46. There may be a loss of a single chromosome-monosomy-or a gain of a chromosome-trisomy. The most common forms of aneuploidy involve chromosome 13, 18, or 21, the latter resulting in Down syndrome. Other aneuploidies may involve the X and Y chromosomes and may actually result in as many as three or four of these sex chromosomes.

As mentioned before, variations in chromosome number consist of aneuploids and euploids. Aneuploids are typically produced by non-disjunction. At the first or second meiotic division (anaphase I or anaphase II), non-disjunction of an X chromosome can result in Turner and Klinefelter syndrome individuals. They frequently result in a change in chromosome number. If a gamete with an extra chromosome (n+1) joins a normal gamete at fertilization, the diploid cell will be 2n+1: this condition is called trisomy. If an abnormal gamete is missing a chromosome, the zygote will be 2n-1: monosomy. Polyploidy is a variation in chromosome number that involves duplication of all the chromosomes in the entire genome. There are two types of polyploidy that exist: autopoplyploidy and allopoplyploidy. Autopolyploidy occurs when the all of the chromosomes in a cell are duplicated, yielding a cell with four copies of each homologous chromosome rather than two copies, called tetraploid (4n). If the chromosome number of a tetraploid were to double again, the result would be an octoploid (8n) cell since there would be eight copies of each chromosome rather than two as in a diploid cell. Autopolyploidy is common in plants such as Chrysanthemum. The basic haploid (n) chromosome number of a diploid species of Chrysanthemum is 9 so cells of these plants contain 18 chromosomes. A closely related tetraploid species has 36 chromosomes that arose by duplication of the 18 chromosomes of a diploid plant. Hexaploid (6n) Chrysanthemum species also occur and were derived by cross pollination of a tetraploid plant with a diploid plant. Autopolyploidy occurs when a cell in the apical meristem of the plant duplicates its chromosomes and begins mitosis; however, in rare cases, these cells fail to divide and simply reenter interphase. The results are cells with a double set of chromosomes in the same nucleus. If such a cell gives rise flowers then diploid gametes will be produced and self-pollination will produce tetraploid offspring.

In comparison to autopolyploidy, allopolyploidy is a form of polyploidy in which the duplicated chromosomes are derived from different but closely related species. They arise when cross-pollination occurs between different, but closely related species of plants. The resulting hybrid plants may be healthy but they are typically sterile because the lack of homology between the two chromosome sets means that appropriate pairing does not occur during meiosis. However, if the chromosome complement in meristem cells of one of these hybrid plants is doubled, the resulting tetraploid cell now has two complete chromosome sets. Fertility is restored because the chromosomes can pair appropriately during meiosis resulting in a new species.

An example of allopolyploidy is cotton. It was was derived from hybridization of two diploid Gossypium species. Interestingly, cotton contains a set of chromosomes from an African species (D genome) and an American species (A genome). It is possible to produce haploid plants that have only a single set of chromosomes. In some species, monoploid plants are produced by regeneration of somatic embryos from pollen precursors called microspores. Monoploid or "haploid" plants are, of course, infertile, but if the chromosomes are doubled, usually by treatment with colchicine, fertility is restored. Since the resulting plants (doubled haploids) are 100% homozygous they are extremely useful for plant geneticists. Due to polyploidy, plants are relatively more tolerant of chromosomal aberrations than are animals are. By analysis of chromosomes of closely related species it is possible to deduce that alterations in chromosome structure and number occur during speciation. For example, of the four chromosomes in the genome of Drosophila melanogaster, chromosomes 2 and 3 are large and metacentric (having the centromere in the median position so that the arms are of equal length). However, in other closely related Drosophilia species, these two large metacentric chromosomes are replaced by four acrocentric chromosomes. Since there is a close correspondence of genetic material on the arms of these chromosomes, it is clear that they are homologous. Similarly, comparison of the 23 pairs of human chromosomes with the 24 pairs of chimpanzee reveals that two acrocentric chromosomes in chimpanzees have apparently fused to form the single metacentric chromosome that is found in humans.

Aneuploids consist of diploid, monosome, trisome, and tetrasome. In comparison, euploids consist of haploid, diploid, triploid, tetraploid, polyploid, autopolyploid, and allopolyploid, all various stages of ploidy, the number of sets of chromosomes per cell. Organisms with complete chromosome sets (either diploid or polyploid) are called euploids (2n) while those that are missing or have extra chromosomes are called aneuploids. With the exception of the sex chromosomes, aneuploidy in animals is almost always lethal. An individual that has one extra chromosome has a condition called trisomy (2n +1) and if one chromosome is missing, the condition is known as monosomy (2n - 1). While organisms with complete duplication of chromosome sets are often healthy and fertile, the loss or gain of a single chromosome can have much more serious effects.

Many disturbances in chromosome number are associated with certain forms of cancer. Most aberrations are "acquired chromosome abnormalities," found in most malignancies; they develop during the formation of cancer. They may be characteristic of a specific tumor. For example, a translocation between chromosomes 9 and 22 is found in chronic myelogenous leukemia, resulting in a characteristic derivative chromosome 22 called the Philadelphia chromosome after the city where it was first discovered four decades ago. Similarly, a translocation between chromosomes 8 and 14 is found in most cases of Burkitt's lymphoma. Also, chromosome number variations are associated with differences in the malignancy of a cancer. For example, a translocation between chromosomes 9 and 22 is a sign of a poor prognosis in acute myelocytic leukemia (AML), whereas a translocation between chromosomes 8 and 21 is a positive sign. Furthermore, disturbances in chromosome number may increase as malignancy advances.

Often times a change in chromosome number is a result of a change in the number of autosomes. An example is down syndrome, which results from trisomy 21: 1 in 1000 live newborns in north America re affected. Most children with down syndrome show mental retardation, and 40% have heart defects. Down syndrome occurs more frequently in children born to older woman but the father's age may also be a factor.

Other changes could be in the number of sex chromosomes. In this case, three conditions can occur: turner syndrome and metafemales, klinefelter syndrome, or XYY condition. Turner syndrome involves females whose cells have only one X chromosome (designated XO). Turner's individuals are sterile and have other phenotypic problems such as premature aging and shorter life expectancy metafemales have three X chromosomes but two are condensed into Barr bodies allowing quite normal development. As for klinefelter syndrome, nondisjunction results in an extra X chromosome in the cells (XXY) of these affected males. Its symptoms include mental retardation and sterility. Finally for the XYY condition, the extra Y chromosome in these males does not affect fertility; instead, it affects individuals that are taller than average and are slightly mentally retarded.