1994 Woodrow Wilson Biology Institute
One way is to map a cytogenetic map in which chromosome bands, each representing 1 million to 5 million bases, are stained and the investigator finds a correlation between people who show a particular trait and exhibit a similar staining pattern. Another way to is produce a physical map using enzymes to cut pieces of DNA into fragments containing markers along with genes whose location is to be determined. By using computers to "walk" or overlay these fragments into their proper sequence we can produce a map of a long strand of DNA. The third technique is a method that has been used for the longest time and the one students will be introduced to here: mapping by crossover frequency.
Genes travel as packaged trains on chromosomes. During meiosis, chromosomes can do some fairly interesting things such as losing pieces (deletion), flipping sections up-side down (inversion), and not separating from their homologous partner when they are supposed to (non- disjunction). Crossover occurs when homologous chromosomes separate towards the end of the prophase I, but are still attached at a few points along their lengths. It is during this attachment that these chromosomes can exchange pieces of their genetic instructions. The frequency of this crossover is directly related to the physical distance that genes are separated from each other on the same chromosome. Genes close to one another have a lower frequency of crossover than do genes farther apart. By keeping records of genetic experiments, such as with Drosophila, we can calculate the crossover frequency, this being the number of times that gene traits should be expressed together, but aren't. In this genetic mapping assignment, I have conjured up imaginary crossover frequencies that allow students to quickly complete the assignment and yet understand the concept of a simple map.
Lewis, Ricki. 1994. Human Genetics. Dubuque, Iowa: Wm. C. Brown Pub.
Gould, Stephen J. 1991. Bully for Brontosaurus. New York: W.W. Norton and Co.
Genes are arranged in a particular order on bodies in the nuclei of cells called chromosomes. Sex cells have to reduce the number of chromosomes from the diploid state to the haploid state. They do this by undergoing a reduction division in which they undergo two divisions. Because chromosomes aren't perfect, they often get tangled with each other, stick together, and snap off to transfer pieces of genetic material to another chromosome during meiosis. This allows for new combinations of genetic material. As a result, genes that should have traveled together as a linked set get separated. By finding the frequency that genes get separated from each other, one can map out the relative position of genes on a chromosome by making a chromosome map. This can be done because the frequency of breaking is a direct result of the physical distance that the genes are located from each other. Genes close to one another on the same chromosome separate less often than genes that are farther apart.
The following data are the results of many experiments that Dr. Chromo de Some has done over many years. All of the listed genes are supposed to be on the same chromosome, but because of crossover to homologous chromosomes these traits are not expressed together as might be expected.
On the other hand, if a sperm containing a Y chromosome comes into contact with the XX combination in the mother's egg, then an XXY male will be produced. This is Klinefelter's syndrome, which is characterized by a sexually underdeveloped boy who has rudimentary testes and prostate glands, often no pubic or facial hair, long arms, and in some instances will develop breast tissue. About one of every 500 males born has Klinefelter's syndrome.
If a male gamete containing the Y chromosome fertilizes an egg containing no X chromosome, then that embryo will fail to develop because it is essential that every human must have at least one X chromosome. There appears to be just too much important genetic information on the X chromosome not to have one.
There are also special cases where, because of non-disjunction again, a woman can have 3 X chromosomes. These women are called triplo-X and can show tallness and have menstrual irregularities. Men who receive an X from their mother and a double Y from their fathers have an XYY combination and have a condition called Jacob's syndrome. When Patricia Jacobs first described this condition in 1965, she proposed the suggestion that the extra Y might cause increased aggression in these men that might land them in trouble with the law. In the early 70's, special counseling was given to these boys and their families to help them to avoid trouble. With continued research it was found that 96% of men with Jacob's syndrome are quite normal, although some may have acne, be a little taller, or may have speech and reading problems. By telling these boys and their families that they might become aggressive to the point of becoming criminals, they often fulfilled these expectations.
There are even special cases where a woman who is XXX and a man who is XYY can make all sorts of combinations in the production of their gametes. It is possible, for example, for an XXX woman to make an XX egg that could join with an XY sperm from an XYY male to produce a child who is XXXY. As you can see, human sex determination and possible polygenetic variations can cover a broad spectrum.
One of the most interesting types of variation in sex chromosomes are those people who show sex reversal in their chromosomal make-up. These are men who appear to be normal men, but have an XX chromosomal combination, and women who appear to be normal women but have the XY combination. These chromosome patterns are reversed from the standard pattern usually seen in mammals, and with your understanding of the crossover phenomenon, you can now understand this unusual situation. On one end of the short Y chromosome, there is a region thought to contain a gene called TDF (testes determining factor) that starts the process of an embryo becoming a boy and also releases an anti-Mullerian hormone (AMH) that suppresses the development of feminine structures. This amounts to only about 1/2 of 1% of the total Y chromosome. This region is called the SRY (sex determining region on the Y chromosome). All humans start off with the same basic body plan (the evolutionist Stephen J. Gould, writing in Bully for Brontosaurus, concludes that this conserves energy within the species and also explains why males have nipples). The genital bud can become either a clitoris or a penis and the gonadal ridge can become either ovary or testes. If the SRY is present, then the process of development leads to a male. If the SRY is absent, then the embryo will become female. If during meiosis the SRY ends up crossing over to the X chromosome, then an XX offspring (normally a female) will end up developing into a male because it has the SRY that causes maleness. Likewise, a Y chromosome that has lost the SRY during crossover will result in an XY individual (normally a male), who because the SRY is lacking will become female. Even if only a small snippet of the Y chromosome crosses over to the X, this sex reversal can occur, provided that the piece that crossed over contained the SRY.