Somatic clone Somatic clone of monosomic of trisomic cells (2n - 1) cells (2n + 1)

3. Trisomy is the gain of a single chromosome, represented as 2n + 1. A trisomic person has 47 chromosomes.

The gain of a chromosome means that there are three homologous copies of one chromosome.

4. Tetrasomy is the gain of two homologous chromosomes, represented as 2n + 2. A tetrasomic person has 48 chromosomes. Tetrasomy is not the gain of any two extra chromosomes, but rather the gain of two homologous chromosomes; so there will be four homologous copies of a particular chromosome.

More than one aneuploid mutation may occur in the same individual. An individual that has an extra copy of two different (nonhomologous) chromosomes is referred to as being double trisomic and represented as 2n + 1 + 1. Similarly, a double monosomic has two fewer nonhomologous chromosomes (2n — 1 — 1), and a double tetrasomic has two extra pairs of homologous chromosomes (2n + 2 + 2).

Effects of Aneuploidy

One of the first aneuploids to be recognized was a fruit fly with a single X chromosome and no Y chromosome, which was discovered by Calvin Bridges in 1913 (see p. 000 in Chapter 4). Another early study of aneuploidy focused on mutants in the Jimson weed, Datura stramonium. A. Francis Blakeslee began breeding this plant in 1913, and he observed that crosses with several Jimson mutants produced unusual ratios of progeny. For example, the globe mutant (having a seedcase globular in shape) was dominant but was inherited primarily from the female parent. When globe plants were self-fertilized, only 25% of the progeny had the globe pheno-type, an unusual ratio for a dominant trait. Blakeslee isolated 12 different mutants ( FIGURE 9.21) that also exhibited peculiar patterns of inheritance. Eventually, John Belling demonstrated that these 12 mutants are in fact trisomics. Datura stramonium has 12 pairs of chromosomes (2n = 24), and each of the 12 mutants is trisomic for a different chromosome pair. The aneuploid nature of the mutants explained the unusual ratios that Blakeslee had observed in the progeny. Many of the extra chromosomes in the tri-somics were lost in meiosis, so fewer than 50% of the gametes carried the extra chromosome, and the proportion of trisomics in the progeny was low. Furthermore, the pollen containing an extra chromosome was not as successful in fertilization, and trisomic zygotes were less viable.

Aneuploidy usually alters the phenotype drastically. In most animals and many plants, aneuploid mutations are lethal. Because aneuploidy affects the number of gene copies but not their nucleotide sequences, the effects of ane-uploidy are most likely due to abnormal gene dosage. Aneuploidy alters the dosage for some, but not all, genes, disrupting the relative concentrations of gene products and often interfering with normal development.

A major exception to the relation between gene number and protein dosage pertains to genes on the mammalian

9.21 Mutant capsules in Jimson weed (Datura stramonium) result from different trisomies. Each type of capsule is a phenotype that is trisomic for a different chromosome.

X chromosome. In mammals, X-chromosome inactivation ensures that males (who have a single X chromosome) and females (who have two X chromosomes) receive the same functional dosage for X-linked genes (see p. 000 in Chapter 4 for further discussion of X-chromosome inactivation). Extra X chromosomes in mammals are inactivated; so we might expect that aneuploidy of the sex chromosomes would be less detrimental in these animals. Indeed, this is the case for mice and humans, for whom aneuploids of the sex chromosomes are the most common form of aneu-ploidy seen in living organisms. Y-chromosome aneuploids are probably common because there is so little information on the Y-chromosome.


Aneuploidy, the loss or gain of one or more individual chromosomes, may arise from the loss of a chromosome subsequent to translocation or from nondisjunction in meiosis or mitosis. It disrupts gene dosage and often has severe phenotypic effects.

Aneuploidy in Humans

Aneuploidy in humans usually produces serious developmental problems that lead to spontaneous abortion (miscarriage). In fact, as many as 50% of all spontaneously aborted fetuses carry chromosome defects, and a third or more of all conceptions spontaneously abort, usually so early in development that the mother is not even aware of her pregnancy. Only about 2% of all fetuses with a chromosome defect survive to birth.

Sex-chromosome aneuploids The most common aneu-ploidy seen in living humans has to do with the sex chromosomes. As is true of all mammals, aneuploidy of the human sex chromosomes is better tolerated than aneu-ploidy of autosomal chromosomes. Turner syndrome and Klinefelter syndrome (see Figures 4.9 and 4.10) both result from aneuploidy of the sex chromosomes.

Autosomal aneuploids Autosomal aneuploids resulting in live births are less common than sex-chromosome aneu-ploids in humans, probably because there is no mechanism of dosage compensation for autosomal chromosomes. Most autosomal aneuploids are spontaneously aborted, with the exception of aneuploids of some of the small autosomes. Because these chromosomes are small and carry fewer genes, the presence of extra copies is less detrimental. For example, the most common autosomal aneuploidy in humans is trisomy 21, also called Down syndrome. The number of genes on different human chromosomes is not precisely known at the present time, but DNA sequence data indicate that chromosome 21 has fewer genes than any other autosome, with perhaps less than 300 genes of a total of 30,000 to 35,000 for the entire genome.

The incidence of Down syndrome in the United States is about 1 in 700 human births, although the incidence is higher among children born to older mothers. People with Down syndrome ( FIGURE 9.22a) show variable degrees of mental retardation, with an average IQ of about 50 (compared with an average IQ of 100 in the general population). Many people with Down syndrome also have characteristic facial features, some retardation of growth and development, and an increased incidence of heart defects, leukemia, and other abnormalities.

Approximately 92% of those who have Down syndrome have three full copies of chromosome 21 (and therefore a total of 47 chromosomes), a condition termed primary Down syndrome ( FIGURE 9.22b). Primary Down syndrome usually arises from random nondisjunction in egg formation: about 75% of the nondisjunction events that cause Down syndrome are maternal in origin, and most arise in meiosis I. Most children with Down syndrome are born to normal parents, and the failure of the chromosomes to divide has little hereditary tendency. A couple who has conceived one child with primary Down syndrome has only a slightly higher risk of conceiving a second child with Down syndrome (compared with other couples of similar age who have not had any Down-syndrome children). Similarly, the couple's relatives are not more likely to have a child with primary Down syndrome.

Most cases of primary Down syndrome arise from maternal nondisjunction, and the frequency of this occur-ing correlates with maternal age ( FIGURE 9.23). Although the underlying cause of the association between maternal age and nondisjunction remains obscure, recent studies have indicated a strong correlation between nondisjunction and aberrant meiotic recombination. Most chromosomes that failed to separate in meiosis I do not show any evidence of having recombined with one another. Conversely, chromosomes that appear to have failed to separate in meiosis II often show evidence of recombination in regions that do

9.22 Primary Down syndrome is caused by the presence of three copies of chromosome 21. (a) A child who has Down syndrome. (b) Karyotype of a person who has primary Down syndrome. (Part a, Hattie Young/Science Photo Library/Photo Researchers; part b, L. Willatt. East Anglian Regional Genetics Service/Science Photo Library/Photo Researchers).

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