13.2 Chromosomal basis of inherited disorders  (Page 2/26)

Disorders in chromosome number

Of all of the chromosomal disorders, abnormalities in chromosome number are the most obviously identifiable from a karyogram. Disorders of chromosome number include the duplication or loss of entire chromosomes, as well as changes in the number of complete sets of chromosomes. They are caused by nondisjunction    , which occurs when pairs of homologous chromosomes or sister chromatids fail to separate during meiosis. Misaligned or incomplete synapsis, or a dysfunction of the spindle apparatus that facilitates chromosome migration, can cause nondisjunction. The risk of nondisjunction occurring increases with the age of the parents.

Nondisjunction can occur during either meiosis I or II, with differing results ( [link] ). If homologous chromosomes fail to separate during meiosis I, the result is two gametes that lack that particular chromosome and two gametes with two copies of the chromosome. If sister chromatids fail to separate during meiosis II, the result is one gamete that lacks that chromosome, two normal gametes with one copy of the chromosome, and one gamete with two copies of the chromosome.

Art connection

Which of the following statements about nondisjunction is true?

1. Nondisjunction only results in gametes with n+1 or n–1 chromosomes.
2. Nondisjunction occurring during meiosis II results in 50 percent normal gametes.
3. Nondisjunction during meiosis I results in 50 percent normal gametes.
4. Nondisjunction always results in four different kinds of gametes.

Aneuploidy

An individual with the appropriate number of chromosomes for their species is called euploid    ; in humans, euploidy corresponds to 22 pairs of autosomes and one pair of sex chromosomes. An individual with an error in chromosome number is described as aneuploid    , a term that includes monosomy    (loss of one chromosome) or trisomy    (gain of an extraneous chromosome). Monosomic human zygotes missing any one copy of an autosome invariably fail to develop to birth because they lack essential genes. This underscores the importance of “gene dosage” in humans. Most autosomal trisomies also fail to develop to birth; however, duplications of some of the smaller chromosomes (13, 15, 18, 21, or 22) can result in offspring that survive for several weeks to many years. Trisomic individuals suffer from a different type of genetic imbalance: an excess in gene dose. Individuals with an extra chromosome may synthesize an abundance of the gene products encoded by that chromosome. This extra dose (150 percent) of specific genes can lead to a number of functional challenges and often precludes development. The most common trisomy among viable births is that of chromosome 21, which corresponds to Down Syndrome. Individuals with this inherited disorder are characterized by short stature and stunted digits, facial distinctions that include a broad skull and large tongue, and significant developmental delays. The incidence of Down syndrome is correlated with maternal age; older women are more likely to become pregnant with fetuses carrying the trisomy 21 genotype ( [link] ).