Chromosome mutations represent large scale modifications to the genome, and may be visualized with a light microscope. They may involve changes in the number of chromosomes or structural modifications of chromosomes.
Changes in chromosome numbers may involve having multiples of the base set of chromosomes which is referred to as euploidy. Euploids may contain multiple sets of chromosomes from a single species, in which case they are referred to as autopolyploids. Or they may contain multiple sets obtained from two species and be referred to as allopolyploids.
Polyploidy creates difficulties during meiosis because of how homologous chromosomes synapse and line up during metaphase I. Often segregation leads to nuclei containing incomplete sets of chromosomes. This is especially prevalent in polyploids that have odd numbers of chromosome sets (e.g., triploids, pentaploids, etc.). Because of this such individuals usually do not engage in sexual reproduction. In general, polyploids are larger than their respective diploid counterparts. These traits are desirable often because large fruited, seedless varieties of plants can be produced. Such plants must be propagated asexually. Autopolyploids are produced experimentally by treating mitotically dividing cells with colchicine. This disrupts spindle formation and results in nonsegregation of chromosomes and the consequent doubling of their number.
Amphidiploids are an allotetraploid (e.g. an organism with the diploid genome of two species).
Aneuploids are individuals that have the incorrect number of chromosomes, but not in complete sets of chromosomes.
Individuals missing a single chromosome are referred to as monosomics. Individuals having one extra chromosome are trisomics. Aneuploids are the result of a nondisjunction occurring during nuclear division. Nondisjunction refers to the situation where the spindle/kinetochore interaction malfunctions and normal segregation does not occur. If nondisjunction occurs during meiosis it is termed primary nondisjunction if it occurs during the first division, and secondary if it occurs during the second division. Aneuploids are frequently inviable because of the genetic inbalance that results due to having 3 messages (or 1 message) for an enzyme that would normally be coded for by one message (diploid individuals). The exception to this in humans is when aneuploidy is the result of sex chromosome nondisjunction. Some examples are females with Turner syndrome (45X) or Triplo-X (47XXX), and males with Klinefelter syndrome (47XXY) of XYY males. No viable monosomies exist for autosomes in humans. The most common trisomy for autosomes results in Down syndrome (47, G21). 95% of cases of Down syndrome are the result of this trisomy. Down syndrome is correlated with maternal age at conception Figure 11-18. Trisomy 13 results in Patau syndrome, and trisomy 18 results in Edwards syndrome. Both of these syndromes have severe phenotypic effects.
Aneuploids are typically quite abnormal for a variety of reasons. Monosomics can potentially express recessive alleles which become hemizygous. However the main problem is that the amount of transcript produced is typically proportional to the number of copies of a gene in a cell. For autosomal aneuploids this creates a genetic imbalance between the transcriptional product for the affected chromosome and other chromosomes. This causes problems in the cells biochemistry. The sex chromosomes generally exhibit adaptations (dosage compensation) to minimize the effect of genetic imbalances because the heterogametic gender always has one less large chromosome than the homogametic gender. In fruit flies, the X chromosome of males is transcribed at a much higher rate than either X chromosome of females. In mammals, one of the X chromosomes of females is inactivated in each mature female’s cell. This inactivation is random and occurs during embryonic development. Individuals having more than two X chromosomes will have all but one inactivated. The inactivated chromosomes become Barr bodies (darkly staining objects seem near the nuclear envelope). The presence of Barr bodies is used for gender identification at international athletic competitions.
Chromosomal rearrangements
Another form of Chromosomal mutation is for organisms to have structurally modified chromosomes. Such modifications are the result of breaks in the double stranded DNA molecules. When such breaks occur the cell has repair systems to ligate the sugar-phosphate backbones together again, but if breaks occur at more than one position then the repair process may fail and rejoin ends together which were not previously nearest neighbors.
Inversions occur when a section of a chromosome is reoriented 1800 relative to its previous orientation. If the centromere is included in the inversion it is called a pericentric inversion, if the centromere is external to the inversion it is called a paracentric inversion. Crossing over within the inverted region, of individuals heterozygous for inversions, leads to inviable gametes (dicentric bridges and acentric fragments in paracentric inversions; duplications and deletions in pericentric inversions). Inversions require a unique synaptic pairing of homologues during prophase I of meisosis called an inversion loop. Pericentric inversions lead to a modification in the arm lengths of chromosomes, but paracentric inversions do not.
Reciprocal translocations occur when regions of nonhomologous chromosomes swap positions due to DNA breakage and incorrect rejoining. Segregation of chromosomes during meiosis leads to gametes having duplications and deletions that are usually fatal.
One half of the gametes will suffer from such deletions and duplications. The reduction in the number of offspring produced is referred to as semisterility.
Whenever an allele assumes a new location in the genome the rate at which transcripts are produced may be affected. This phenomenon is referred to as a position effect. The most common cause of position effects is that an allele that previously existed in a euchromatic region is repositioned near to a heterochromatic region.
Deletions can be intragenic (within a gene) or multigenic (including multiple genes) in nature. Intragenic deletions represent null mutations for that gene. Often multigenic deletions are lethal due to gene balance. Individuals heterozygous for deletions must form deletion loops to synapse during prophase I of meiosis. Non-deleted regions homologous to deleted regions will be phenotypically expressed whether they are recessive or dominant, so are effectively hemizygous. Recessive alleles in these regions are said to express pseudodominance.
Duplications can be located adjacent to each other and called tandem duplications or be separated in the genome and then referred to as insertional duplications. Individuals heterozygous for duplications will form loops during synapsis. Duplications have been very important evolutionarily because mutations can accumulate at one of the loci containing the duplication while wild type performance is maintained at the other locus. This allows a lineage to persist following the occurrence of what would otherwise be a deleterious mutation until other mutations accumulate modifying the genes role into something more advantageous. Patterns such as this lead to gene families.
Inversions permit allelic combinations to remain linked for a considerable time if they occur within the inversion. Therefore if advantageous combinations of alleles arise in these inversions, they may be past on to future generations as a set.