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OBJECTIVES
After studying this chapter, you should be able to:
Appreciate that the roughly 3 × 109 base pairs of DNA that compose the haploid genome of humans are divided uniquely between 23 linear DNA units, the chromosomes. Humans, being diploid, have 23 pairs of these linear chromosomes: 22 autosomes and two sex chromosomes.
Understand that human genomic DNA, if extended end-to-end, would be meters in length, yet still fits within the nucleus of the cell, an organelle that is only microns (μ; 10−6 meters) in diameter. Such condensation in DNA length, in part, is induced following its association with the highly positively charged histone proteins resulting in the formation of a unique DNA-histone complex termed the nucleosome. Nucleosomes have DNA wrapped around the surface of an octamer of histones.
Explain that strings of nucleosomes form along the linear sequence of genomic DNA to form chromatin, which itself can be more tightly packaged and condensed, this ultimately leads to the formation of the chromosomes.
Appreciate that while the chromosomes are the macroscopic functional units for DNA transcription, replication, recombination, gene assortment, and cellular division, it is DNA function at the level of the individual nucleotides that composes regulatory sequences linked to specific genes that are essential for life.
Describe the steps, phase of the cell cycle, and the molecules responsible for the replication, repair, and recombination of DNA, and understand the negative effects that errors in any of these processes can have upon cellular and organismal integrity and health.
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BIOMEDICAL IMPORTANCE
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The genetic information in the DNA of a chromosome can be transmitted by exact replication or it can be exchanged by a number of processes, including crossing over, recombination, transposition, and gene conversion*. These processes provide a means of ensuring adaptability and diversity for the organism, but when they go awry, can also result in disease. A number of enzyme systems are involved in DNA replication, alteration, and repair. Mutations are due to a change in the base sequence of DNA and may result from the faulty replication, transposition, or repair of DNA and occur with a frequency of about one in every 106 cell divisions. Abnormalities in gene products (either in RNA, protein function, or amount) can be the result of mutations that occur in transcribed protein coding, and nonprotein coding DNA, or nontranscribed regulatory-region DNA. A mutation in a germ cell is transmitted to offspring (so-called vertical transmission of hereditary disease). A number of factors, including viruses, chemicals, ultraviolet light, and ionizing radiation, increase the rate of mutation. Mutations often affect somatic cells and so are passed on to successive generations of cells, but only within an organism (ie, horizontally). It is becoming apparent that a number of diseases—and perhaps most cancers—are due to the combined effects of vertical transmission of mutations as well as horizontal transmission of induced mutations.
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