Chapter 17 - Large-scale Chromosomal Changes

• No records of the birth, which occurred early in the twentieth century, are available, but the couple knows of no other cases of Down syndrome in their families.
• The couple decides to have children.
• Gene mutations are changes that take place within a gene, whereas chromosome mutations are changes in a chromosome region encompassing multiple genes.
• The ability to sequence whole genomes has enabled the discovery of inversions that are not cytologically visible and revealed that many inversions exist both within and between species.
• Inversions can be detected microscopically through new arm ratios.
• Inversions affect recombination in another way, too, by causing mechanical pairing problems in the region of the inversion and causing a large distortion that reduces the opportunity for crossing over in the neighboring regions.
• Inversions can also affect recombination by reducing the expected recombinant frequency in a dihybrid testcross.
• The phenotypic consequences of these inversions are not known, but such inversions have been proposed to play key roles in forming and maintaining reproductive barriers between species.
• Paracentric inversions do not alter the arm ratio, but they may be detected microscopically by observing changes in banding or other chromosomal landmarks, if available.
• Pericentric inversions can be detected microscopically through changes in banding or other chromosomal landmarks, if available.
• Gene mutations are never detectable microscopically; a chromosome bearing a gene mutation looks the same under the microscope as one carrying the wild-type allele.
• A translocation moves a chromosome segment to another position in the genome.
• Inversion heterozygotes show inversion loops at meiosis, and crossing over within the loop results in inviable products.
• Many human chromosome disorders are associated with regions of the genome that harbor segmental duplications.
• A simple example of a translocation is a reciprocal translocation, in which parts of nonhomologous chromosomes exchange positions.
• An inversion is a 180-degree turn of a part of a chromosome.
• The crossover products of pericentric inversions, which span the centromere, differ from those of paracentric inversions, which do not, but both show reduced recombinant frequency in the affected region and often result in reduced fertility.
• In the heterozygous state, translocations produce duplication-and- deletion meiotic products, which can lead to unbalanced zygotes.
• Chromosomal rearrangements are also substrates for evolution and useful in engineering special strains of organisms for experimental and applied genetics.
• New gene linkages can be produced by translocations.
• The random segregation of centromeres in a translocation heterozygote results in 50 percent unbalanced meiotic products and, hence, 50 percent sterility (semisterility).
• In the homozygous state, inversions may cause little problem for an organism unless one of the breaks disrupts a gene.
• Some cells in triploid mammals are found to have one active X, whereas others, surprisingly, have two.
• The lower level of “functional aneuploidy” in XXX than in XXY, plus the fact that the active X genes appear to lead to feminization, may explain the feminized phenotype of XXY males.
• The severity of Turner syndrome (XO) may be due to the deleterious effects of monosomy and to the lower activity of the transcribed genes of the X (compared with XX) females.
• Most die in utero.
• Similarly, an XXY male is only moderately affected because only one of his two X chromosomes is active in each cell.
• In XXX females, the few transcribed genes are active at only 1.5 times the level that they are in XX females.
• Human polyploid zygotes do arise through various kinds of mistakes in cell division.
• In XXY males, the genes scattered throughout an “inactive X” are transcribed at twice the level that they are in XY males.
• Part of the rule for gene balance in organisms that have a single active X seems to be that there must be one active X for every two copies of the autosomal chromosome complement.
• As is usually observed for aneuploids, monosomy for the X chromosome produces a more abnormal phenotype than does having an extra copy of the same chromosome (triplo-X females or XXY males).
• Gene dosage is also important in the phenotypes of polyploids.
• This fact seems to violate the principle that polyploids are more normal than aneuploids.
• Pericentric inversions and translocations generate products of meiosis that contain a duplication and a deletion.
• Human chromosome 2 is the result of a fusion between two chromosomes, represented by chromosomes 12 and 13 in the chimpanzee genome.
• Duplications and deletions are useful for a variety of experimental applications, including the mapping of genes and the varying of gene dosage for the study of regulation.
• Any recombination between these genes would create hybrid wing patterns that might no longer be recognized as distasteful by predators, and thus increase the risk that the butterfly would be eaten.
• Chromosome rearrangements, such as inversions, might actually facilitate evolutionary change, as seen in this chapter.
• Müllerian mimicry in butterflies is an example of how chromosome rearrangements can facilitate evolutionary change.