At this point in the course, we have a fundamental understanding of how genes are arrayed along chromosomes and how they get passed along during cell division. Mitotic cell divisions, maintaining the diploid state, occur throughout the body of an individual to build and replenish the tissues and organs. Meiotic cell divisions occur to produce the haploid gametes (egg or sperm in animals) that can subsequently participate in sexual fertilization to produce the next generation. During meiosis, random alignment of homologous chromosome pairs (bivalents) in meiotic metaphase I results in independent assortment, thus ensuring that the haploid gametes are of various genotypes. ( In humans, independent assortment during meiosis I produces about 8 million equally likely gamete genotype possibilities; i.e., 2 to the 23'rd power ). In addition, random crossing-over between homologous chromatids during meiotic prophase I is an inherent part of the process of meiosis, and this generates even more genetic variety in the population of gametes.

1. What is the most basic system of designating locations along human chromosomes?

Figures 8.1 and 8.2 show photographs of (a) mitotic metaphase spreads of chromosomes and (b) the resulting "karyotype" from a human male. Figure 8.3 shows a representation of the characteristic visible banding patterns seen in Giemsa-stained condensed human chromosomes, and how these visible bands have provided the basis for describing any general location along any of the human chromosomes. So, for example, you might say "I am studying the function of a gene that is at locus 15q22.3".
The human "blood group gene" we studied earlier as an example of co-dominance is at locus 9q34.

2. At the chromosomal level, how does our genome compare with the genomes of our closest evolutionary relatives?

Our closest living primate relatives (chimps, gorillas, and orangutans) have a chromosome composition that is almost the same as ours. The most noticeable difference is that these primates have a haploid chromosome number of 24 compared to our 23. These primates have two "acrocentric" chromosomes we do not have, but they are missing our "metacentric" chromosome #2. At the genetic map level, these two acrocentric primate chromosomes are extremely similar to the two arms of our chromosome #2 (i.e., they have essentially the same genes at the same locations). So, it's pretty clear that at some point during our evolutionary divergence from the other primates, the two acrocentric chromosomes fused together to become our chromosome #2, as shown in Figure 8.6.

3. What are the major human chromosome abnormalities?

Page 309 of textbook: "Approximately 15 percent of all recognized pregnancies in human beings terminate in spontaneous abortion, and in about half of all spontaneous abortions, the fetus has a major chromosome abnormality."

Table 8.2 shows what these chromosomal abnormalities are, and how often they show up in fetuses that abort or proceed to live birth.

"Polyploidy" occurs in about 1 to 2% of human fetuses, but no polyploid babies ever make it to birth. In general, polyploidy is essentially never seen in vertebrates. Among animals as a whole, polyploidy is seen in some insects. (Textbook, page 311: "For example, in Drosophila, triploid females are viable, fertile, and nearly normal in morphology.") Among plants, polyploidy is quite common, being the actual case for about 1/3 of all flowering plants, as well as for such cultivated plants as bananas, oats, cotton, potatoes, coffee, sugar cane, and wheat (Textbook pages 329-336).

"Aneuploidy" (diploid chromosome number other than the normal 46) occurs in about 5% of human fetuses, and sometimes results in live birth. Trisomy of an autosome occurs in about 4% of human fetuses. Most of these never result in live birth, except for trisomy of chromosomes 13, 18, or 21. Trisomy 21 leads to live birth about 1/3 of the time, but these babies have the condition called Down syndrome.

The four most common abnormalities involving numbers of human sex chromosomes are shown below (and in Table 8.2). As we have seen already, the most common way for situations like these, as well as autosomal trisomy, to arise is nondisjunction in either meiosis I or II during gamete production.

47 XXX (Trisomy-X) people are female, usually phenotypically normal. ( page 314)
47 XYY (Double-Y) people are male, usually phenotypically normal.
47 XXY (Klinefelter syndrome) people are male, but do not mature sexually.
45 X (Turner syndrome) people are female, but do not mature sexually.

Table 8.2 shows that 45 X is by far the most common of these in fetuses, but 99% of 45 X's end up as spontaneous abortions. Similarly, as your book points out on page 311, monosomy for any of the autosomes essentially never shows up in recognized human pregnancies because such cases abort spontaneously very early in the pregnancy.

4. How does trisomy for chromosome 21 happen?

Trisomy 21 occurs when one of the gametes results from a meiosis in which chromosome 21 nondisjunction occurred during either meiosis I (about 80% of cases) or meiosis II (about 20% of cases), giving rise to two (rather than one) chromosomes 21 in this gamete. At fertilization, the other gamete supplies the third #21.

The probability of such nondisjunction occurring during gamete production is low in young adults. For women, however, the risk of nondisjunction occurring during egg production goes up dramatically with age. Figure 8.12 shows the results of a study of all births in Sweden over a two year period.