The first four chapters have taken a long-range view of the way in which genes determine a phenotype through interconnected biochemical pathways and cell interactions. In this chapter we will focus on how the genetic information packaged in chromosomes is duplicated and distributed during cell division (Figure 5-1). Then in Chapter 6, we will explore how chromosome behavior during the formation and fusion of gametes determines the predictable genetic outcomes of a mating.
A chromosome spread (unsorted) with fluorescent probes for chromosome number 14. A nondividing cell is off to the side also showing the chromosome 14 probes. (Reprinted with permission from Brooker RJ: Genetics: Analysis & Principles, 3rd ed. New York: McGraw-Hill, 2008.)
The process of nuclear division is very accurate. Yet, errors do occur and can lead to changes in chromosome number and structure with often severe or even fatal consequences. It is not easy to study the genetic control of nuclear division at more than a descriptive level. This is because some of the most powerful tools available to a genetic researcher are mutations. By seeing how a mutation alters a process, one can deduce the role of the normal gene. But mutations are difficult to isolate for the molecular and biochemical events governing mitosis, which is the complete duplication of the genome of a cell to produce two identical cells, and meiosis, which is the reduction division found in egg- and sperm-forming tissue. In order to collect and analyze the roles of mutations in a given trait, one must be able to breed and manipulate them. But mutations that prevent nuclear division naturally block that approach, forcing researchers to find new ways to explore the molecular control of genetic transmission. Most medical applications, however, simply depend upon understanding the inherent logic of mitosis and meiosis and the consequences of errors or other complications that affect them. That will be our focus in this chapter.
In addition to errors in nuclear division that lead to changes in chromosome number, various agents like radiation can alter chromosome structure. Changes in structure affect a block of genes and influence many otherwise independent biochemical processes. They can also cause complicated physical interactions between chromosomes that have serious secondary consequences. In this chapter we will first discuss the normal processes of chromosomal distribution in mitosis and meiosis, and then explore the kinds of errors that affect chromosome number and structure. There are many important medical examples of each.
Part 1: Background and Systems Integration
Overview of Nuclear Division as an Information Distribution System
Some of the basic terminology used to describe the genome was introduced in the first two chapters. We know, for example, that the nucleus of a diploid (2n) ...