Written Assignment 2

Reproduction becomes riskier for women as they become older. Increasingly, their gametes contain incorrect numbers of chromosomes or chromosomes that have been damaged (Figure 8-31). These problems can lead to adverse effects on the offspring that range from minor to fatal.

Parents can request a quick test for some common genetic problems even before their baby is born. This information is available from an analysis of an individual’s karyotype, a visual display of the complete set of chromosomes. A karyotype can be made for adults or children, but it is most commonly done for a fetus. A karyotype is a useful diagnostic tool because it can be prepared very early in the fetus’s development to assess whether it has an abnormality in the number of chromosomes or in their structure. And because the test shows all of the chromosomes, even the sex chromosomes, it also reveals the sex of the fetus.

Preparing a karyotype takes five steps. (1) Cells are obtained from the individual. (2) The cells are cultured in a test tube with nutrients so that they divide. (3) After a period of cell division, the cells are treated with a chemical that stops them exactly midway through cell division—a time when the chromosomes are coiled thickly and are more visible than usual. (4) The cells are then placed on a microscope slide, and a stain is added that binds to the chromosomes, making them even more visible. (5) Finally, the chromosomes are arranged by size and shape and displayed on a monitor, where they can be assessed (Figure 8-32).

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Collecting cells from a fetus is more challenging than taking a small blood sample, as is typical for testing adults and children. Two different methods can be used for collecting fetal cells. 1. Amniocentesis. A needle is inserted into the amniotic sac and fluid is removed. 2. Chorionic Villus Sampling (CVS). In this procedure, rather than sampling cells from the amniotic fluid, a small bit of tissue is removed from the placenta.

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The resulting karyotype, whether from amniocentesis or CVS, will reveal whether the fetus carries an extra copy of any of the chromosomes or is perhaps lacking a copy of one or more chromosomes. Of all the chromosomal disorders detected by karyotyping, Down syndrome is the most commonly observed. Named after John Langdon Down, the doctor who first described it in 1866, it is revealed by the presence of an extra copy of chromosome #21. (For this reason, the condition that causes Down syndrome is also called “trisomy 21.”) Affecting about 1 in every 1,000 children born, Down syndrome is characterized by a suite of physical and mental characteristics that includes learning disabilities, a flat facial profile, heart defects, and increased susceptibility to respiratory difficulties.

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Down syndrome and other disorders caused by a missing chromosome or an extra copy of a chromosome are a consequence of nondisjunction, the unequal distribution of chromosomes during cell division. Nondisjunction can occur at two different points in meiosis: when homologues fail to separate during meiosis I, or when sister chromatids fail to separate during meiosis II (Figure 8-35). In both cases, nondisjunction results in an egg or sperm with zero or two copies of a chromosome rather than a single copy. Any of the chromosomes can fail to separate during cell division, but the ramifications of trisomy (having an extra copy of one chromosome in every cell) are greater for chromosomes with larger numbers of genes. When trisomy occurs for chromosomes with greater numbers of genes, the likelihood that the developing embryo will survive to birth is reduced. Consequently, we tend to see cases of trisomy that involve only the chromosomes with the fewest genes, such as chromosomes 13, 15, 18, 21, and 22. In fact, observations show that trisomy 1 is never seen (all such fertilized eggs die before implantation in the uterus), trisomy 13 occurs in 1 in 20,000 newborns (and most die soon after birth), while trisomy 21, as we’ve seen, occurs in 1 in 1,000 newborns (many of whom live long lives). As women become older there are increased problems associated with reproduction. As women age, their gametes tend to have more errors. The reason is that the eggs began meiosis near the time the woman was born, and they may not complete it until she is 40 or more years old. During those decades, the cells may develop problems—including a reduction in the size and stability of the spindle fibers and reduced cohesion between sister chromatids—that interfere with normal cell division. In men, the cells that undergo meiosis are relatively young because new sperm-producing cells are produced every couple of weeks after puberty. Whereas lacking a non-sex chromosome or having an extra chromosome usually has serious consequences for health, we’ll see in the next section that lacking or having an extra X or Y chromosome has consequences that are much less severe.

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It is usually fatal to have one too many or one too few of the non-sex chromosomes. However, many individuals are born lacking one of the sex chromosomes or having an additional X or Y chromosome, and they usually survive. In each of the following cases, the condition is caused by nondisjunction of the sex chromosomes during the production of sperm or eggs (Figure 8-36). Turner syndrome: Approximately 1 in 5,000 females carry only one X chromosome (and no Y chromosome), exhibiting a condition called Turner syndrome, denoted as X_ (or sometimes XO). This is the only condition in humans in which a person can survive without one of a pair of chromosomes. Instead of having 46 chromosomes in every cell, these individuals have only 45. As common as Turner syndrome is, in 98% of the fertilized eggs in which this condition occurs, the embryo is spontaneously aborted long before a fetus can come to term. There are both physical and mental consequences of the absence of a second sex chromosome. • Women with Turner syndrome are usually relatively short, averaging 4 feet 8 inches in height. • They develop a web of skin between the neck and shoulders. • The ovaries never fully mature, so the women are almost always sterile. • The breasts and other secondary sex characteristics develop incompletely. • Intelligence is usually normal, but some learning difficulties are common. Klinefelter syndrome: An individual who carries two X chromosomes and a Y chromosome, a condition known as Klinefelter syndrome, develops as a male. This is because, as we saw earlier, the Y chromosome carries genetic instructions that cause fetal gonads to develop as testes; if these instructions are absent, the fetal gonads develop as ovaries. The extra X chromosome, however, does cause males with Klinefelter syndrome to be somewhat feminized, although this effect can be reduced through treatments such as testosterone supplementation. Approximately 1 in 1,000 males have the genotype XXY, making this one of the most common genetic abnormalities in humans. Klinefelter syndrome has some physical and mental consequences. • Men with this syndrome have testes that are smaller than average. Because the testes are small, levels of

testosterone are low, and the men are almost always infertile. • They develop some female features, including reduced facial and chest hair and some breast development. • They have long limbs and are slightly taller than average (about 6 feet on average). • They learn to speak at a later age than average and tend to have language impairments. • Some individuals have further additional X chromosomes, with the karyotypes XXXY or even XXXXY. These

males also exhibit the symptoms of Klinefelter syndrome but more frequently have mental retardation. A hermaphrodite is an individual with functioning male and female reproductive organs capable of producing both male and female gametes. Often it is mistakenly assumed that a person with Klinefelter syndrome must be a hermaphrodite because he has both two X chromosomes (which would usually make an individual a female) and an X and a Y chromosome (usually making the individual a male). Hermaphroditism is common among invertebrates and occurs in some fish and other vertebrates, but contrary to urban legends, human hermaphrodites do not exist. Some men with Klinefelter syndrome may have some features of the opposite sex; however, they do not produce female gametes and so are not hermaphrodites. Individuals with sex characteristics that preclude definitive identification as male or female are called “intersex.”

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XYY Males: There is no official name for the condition in which an individual has one X chromosome and two Y chromosomes. This chromosomal abnormality occurs in approximately 1 in 1,000 males (and in about 1 in 325 males who are 6 feet or taller). There are no distinguishing features at birth to indicate that an individual carries an extra Y chromosome, and the vast majority of affected individuals live their lives without even knowing they have an extra chromosome in every cell. Several consequences of the XYY condition have been well documented, including taller than average height, moderate to severe acne, and potentially lower than average intelligence. Although an error during meiosis in either the father or the mother can cause Klinefelter or Turner syndrome, it is only an error in meiosis in a male that can give rise to an XYY child. Why? Because only males carry Y chromosomes. Consequently, an XYY child must have received both of his Y chromosomes from his father. This means that the father’s sperm cell must have contained two copies of the Y, a result of nondisjunction during meiosis in the father. XXX Females: Individuals with three X chromosomes occur at a frequency of about 1 in 1,000 women. Very few studies of this condition have been completed, although initial observations suggest that XXX females are slightly taller than average but have no obvious physical or intellectual problems. In contrast to individuals who have Turner syndrome, most XXX females are fertile.

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