4.10 Persons with Turner syndrome have a single X chromosome in their cells. (a) Characteristic physical features. (b) Chromosomes from a person with Turner syndrome. (Part a, courtesy of Dr. Daniel C. Postellon, Devos Children's Hospital; Part b, Dept. of Clinical Cytogenics, Addenbrookes Hospital/Science Photo Library/Photo Reseachers.)
secondary sex characteristics remain immature: menstruation is usually absent, breast development is slight, and pubic hair is sparse. This syndrome is seen in 1 of 3000 female births. Affected women are frequently short and have a low hairline, a relatively broad chest, and folds of skin on the neck ( Figure 4.10). Their intelligence is usually normal. Most women who have Turner syndrome are sterile. In 1959, C. E. Ford used new techniques to study human chromosomes and discovered that cells from a 14-year-old girl with Turner syndrome had only a single X chromosome; this chromosome complement is usually referred to as XO.
There are no known cases in which a person is missing both X chromosomes, an indication that at least one X chromosome is necessary for human development. Presumably, embryos missing both Xs are spontaneously aborted in the early stages of development.
triple-X females is slightly greater than in the general population, but most XXX females have normal intelligence. Much rarer are women whose cells contain four or five X chromosomes. These women usually have normal female anatomy but are mentally retarded and have a number of physical problems. The severity of mental retardation increases as the number of X chromosomes increases beyond three.
The role of sex chromosomes The phenotypes associated with sex-chromosome anomalies allow us to make several inferences about the role of sex chromosomes in human sex determination.
Klinefelter syndrome Persons who have Klinefelter syndrome, which occurs with a frequency of about 1 in 1000 male births, have cells with one or more Y chromosomes and multiple X chromosomes. The cells of most males having this condition are XXY, but cells of a few Klinefelter males are XXXY, XXXXY, or XXYY. Persons with this condition, though male, frequently have small testes, some breast enlargement, and reduced facial and pubic hair ( FIGURE 4.11). They are often taller than normal and sterile; most have normal intelligence.
Poly-X females In about 1 in 1000 female births, the child's cells possess three X chromosomes, a condition often referred to as triplo-X syndrome. These persons have no distinctive features other than a tendency to be tall and thin. Although a few are sterile, many menstruate regularly and are fertile. The incidence of mental retardation among
1. The X chromosome contains genetic information essential for both sexes; at least one copy of an X chromosome is required for human development.
2. The male-determining gene is located on the Y chromosome. A single copy of this chromosome, even in the presence of several X chromosomes, produces a male phenotype.
3. The absence of the Y chromosome results in a female phenotype.
4. Genes affecting fertility are located on the X and Y chromosomes. A female usually needs at least two copies of the X chromosome to be fertile.
5. Additional copies of the X chromosome may upset normal development in both males and females, producing physical and mental problems that increase as the number of extra X chromosomes increases.
4.11 Persons with Klinefelter syndrome have a Y chromosome and two or more X chromosomes in their cells. (a) Characteristic physical features. (b) Chromosomes of a person with Klinefelter syndrome.
(Part a, to come; part b, Biophoto Associates/Science Source/ Photo Researchers.)
The male-determining gene in humans The Y chromosome in humans and all other mammals is of paramount importance in producing a male phenotype. However, scientists discovered a few rare XX males whose cells apparently lack a Y chromosome. For many years, these males presented a real enigma: How could a male phenotype exist without a Y chromosome? Close examination eventually revealed a small part of the Y chromosome attached to another chromosome. This finding indicates that it is not the entire Y chromosome that determines maleness in humans; rather, it is a gene on the Y chromosome.
Early in development, all humans possess undifferenti-ated gonads and both male and female reproductive ducts. Then, about 6 weeks after fertilization, a gene on the Y chromosome becomes active. By an unknown mechanism, this gene causes the neutral gonads to develop into testes, which begin to secrete two hormones: testosterone and Mullerian-inhibiting substance. Testosterone induces the development of male characteristics, and Mullerian-inhibiting substance causes the degeneration of the female reproductive ducts. In the absence of this male-determining gene, the neutral gonads become ovaries, and female features develop.
In 1987, David Page and his colleagues at the Massachusetts Institute of Technology located what appeared to be the male-determining gene near the tip of the short arm of the Y chromosome. They had examined the DNA of several XX males and XY females. The cells of one XX male that they studied possessed a very small piece of a Y chromosome attached to one of the Xs. This piece came from a section, called 1A, of the Y chromosome. Because this person had a male phenotype, they reasoned that the male-
determining gene must reside within the 1A section of the Y chromosome.
Examination of the Y chromosome of a 12 year-old XY girl seemed to verify this conclusion. In spite of the fact that she possessed more than 99.8% of a Y chromosome, this XY person had a female phenotype. Page and his colleagues assumed that the male-determining gene must reside within the 0.2% of the Y chromosome that she was missing. Further examination showed that this Y chromosome was indeed missing part of section 1A. They then sequenced the DNA within section 1A of normal males and found a gene called ZFY, which appeared to be the testis-determining factor.
Within a few months, however, results from other laboratories suggested that ZFY might not in fact be the male-determining gene. Marsupials (pouched mammals), which also have XX-XY sex determination, were found to possess a ZFY gene on an autosomal chromosome, not on the Y chromosome. Furthermore, several human XX males were found who did not possess a copy of the ZFYgene.
A new candidate for the male-determining gene, called the sex-deter mining region Y (SRY) gene, was discovered in 1990 ( Figure 4.12). This gene is found in XX males and is missing from all XY females; it is also found on the Y chromosome of all mammals examined to date. Definitive proof that SRY is the male-determining gene came when scientists placed a copy of this gene into XX mice by means of genetic engineering. The XX mice that received this gene, although sterile, developed into anatomical males.
The SRYgene encodes a protein that binds to DNA and causes a sharp bend in the molecule. This alteration of DNA structure may affect the expression of other genes that
Short arm Centromere
Sex-determining region Y
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