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Chromosomal Abnormalities - Normal Number And Structure Of Human Chromosomes, Normal Cell Division, Alterations In Chromosome Structure, Genetic Counseling - Alterations in chromosome number

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Chromosome abnormalities describe alterations in the normal number of chromosomes or structural problems within the chromosomes themselves. Both kinds of chromosome abnormalities may result from an egg (ovum) or sperm cell with the incorrect number of chromosomes, or with a structurally faulty chromosome uniting with a normal egg or sperm during conception.

Some chromosome abnormalities may occur shortly after conception. In this case, the zygote, the cell formed during conception that eventually develops into an embryo, divides incorrectly. Other abnormalities may lead to the death of the embryo. Zygotes that receive a full extra set of chromosomes, a condition called polyploidy, usually do not survive inside the uterus, and are spontaneously aborted (a process sometimes called a miscarriage).

Chromosomal abnormalities can cause serious mental or physical disabilities. Down syndrome, for instance, is caused by an extra chromosome 21 (trisomy 21). People with Down syndrome are usually mentally retarded and have a host of physical defects, including heart disorders. Other individuals, called Down syndrome mosaics, have a mixture of normal cells and cells with three copies of chromosome 21, resulting in a mild form of the disorder.


Two kinds of chromosome number defects can occur in humans: aneuploidy, an abnormal number of chromosomes, and polyploidy, more than two complete sets of chromosomes.


Aneuploidy

Most alterations in chromosome number occur during meiosis. During normal meiosis, chromosomes are distributed evenly among the four daughter cells. Sometimes, however, an uneven number of chromosomes are distributed to the daughter cells. As noted in the previous section, chromosome pairs may not move apart in meiosis I, or the chromosomes may not separate in meiosis II. The result of both kinds of mistakes (called nondisjunction of the chromosomes) in that one daughter cell receives an extra chromosome, and another daughter cell does not receive any chromosome.

When an egg or sperm that has undergone faulty meiosis and has an abnormal number of chromosomes unites with a normal egg or sperm during conception, the zygote formed will have an abnormal number of chromosomes. This condition is called aneuploidy. There are several types of aneuploidy. If the zygote has an extra chromosome, the condition is called trisomy. If the zygote is missing a chromosome, the condition is called monosomy.

If the zygote survives and develops into a fetus, the chromosomal abnormality is transmitted to all of its cells. The child that is born will have symptoms related to the presence of an extra chromosome or absence of a chromosome.

Examples of aneuploidy include trisomy 21, also known as Down syndrome that occurs approximately 1 in 700 newborns, Trisomy 18 also called Edward syndrome (1:3500) and trisomy 13, also called Patau syndrome (1:5000). Trisomy 18 and 13, are more severe than of Down syndrome. Prenatal ultasound anomalies of fetuses affected by Down syndrome include nuchal thickening, duodenal stenosis, short femur and many other. Children with trisomy 21 have the characteristic face with a flat nasal bridge, epicanthic folds, protruding tongue and small ears. Among possible malforamations cleft palates, hare lips, and cardiac malformations (atrial and ventricular septal, and atriventricular canal defects). Mental retardation is always present at various degree. The life span once the individual has survived ranges between 50 and 60 years. Trisomy 18, known as Edwards' syndrome, results in severe multi-system defects. Most trisomies 18 results in spontaneous abortion. Affected infants have a small facies, small ears, overlapping fingers and rocker-bottom heels. Cardiac and other internal malformations are very frequent. Newborns with trisomy 13 have midline anomalies as well as scalp cutis aplasia, brain malformations, cleft lip and or palate, omphalocele and many others. Polydactyly is also frequent. Children with trisomy 13 and trisomy 18 usually survive less than a year after birth and are more likely to be females (Figure 1).


Aneuploidy of sex chromosomes

Sometimes, nondisjunction occurs in the sex chromosomes. Humans have one set of sex chromosomes. Figure 1. Karyotype from a child with trisomy 13 (a) or trisomy 18 (b). Illustration by Hans & Cassidy. Courtesy of Gale Group. These sex chromosomes are called "X" and "Y" after their approximate shapes in a karyotype. Males have both an X and a Y chromosome, while females have two X chromosomes. Remarkably, abnormal numbers of sex chromosomes usually result in less severe defects than those that result from abnormal numbers of the other 22 pairs of chromosomes. The lessened severity may be due Figure 2. Aneuploidy of sex chromosomes. Illustration by Hans & Cassidy. Courtesy of Gale Group. to the fact that the Y chromosome carries few genes, and any extra X chromosomes become inactivated shortly after conception. Nevertheless, aneuploidy in sex chromosomes causes changes in physical appearance and in fertility (Figure 2).

In Klinefelter's syndrome, for instance, a male has two X chromosomes (XXY). This condition occurs in 1 out of every 2,000 births (1:800 males about). Men with Klinefelter's syndrome have small testes and are usually sterile. They also have female sex characteristics, such as enlarged breasts (gynecomastia). Males who are XXY are of normal intelligence or affected by a mild delay or behavioural immaturity. However, males with more than two X chromosomes, such as XXXY, XXXXY, or XXXXXY are mentally retarded.

Males with an extra Y chromosome (XYY) have no physical defects, although they may be taller than average. XYY males occur in 1 out of every 2,000 births (1:800 males about). It is not associated with increased aggressive and criminal behaviour as initially thought.

Females with an extra X chromosome (XXX) are called metafemales. This defect occurs in 1 out of every 800 females Metafemales have lowered fertility (oligomenorrhea and premature menopause), but their physical appearance is normal.

Females with only one X chromosome (XO) have Turner syndrome. Turner syndrome is also called monosomy X and occurs in 1 out of every 5,000 births (1:2,500 females). People with Turner syndrome have sex organs that do not mature at puberty and are usually sterile. They are of short stature and have no mental deficiencies.

Uniparental disomy is the presence in a diploid cell line of both chromosomes of a given pair from only one of the two parents. Possible consequence of uniparental disomy include imprinting of single genes (abnormal levels of gene product), homozygosity for mutant alleles. Microdeletion syndromes associated to a disomy of the chromosome 15 include Prader-Willi (maternal disomy) and Angelman Syndrome (patermal disomy).


Polyploidy

Polyploidy is lethal in humans. Normally, humans have two complete sets of 23 chromosomes. Normal human cells, other than sex cells, are thus described as diploid. Two polyploid conditions occur in humans. Triploidy ( three set of chromosomes that results in 69 chromosomes with XXX, XXY or XYY sex chromosome) and tetrapolidy (92 chromosome and either XXXX or XXYY sex chromosome). Triploidy could result from the fertilization of an abnormal diploid sex cell with a normal sex cell. Tetraploidy could result from the failure of the zygote to divide after it replicates its chromosomes. Human zygotes with either of these conditions usually die before birth, or soon after. Interestingly, polyploidy is common in plants and is essential for the proper development of certain stages of the plant life cycle. Also, some kinds of cancerous cells have been shown to exhibit polyploidy. Rather than die, the polyploid cells have the abnormally accelerated cell division and growth characteristic of cancer.


Chromosome - Dna And Protein Synthesis, Genes, Chromosome Numbers, Chromosome Shape, The Role Of Proteins In Packaging Dna [next]

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