Genetics Index Glossary

Overview of Chromosomal Disease


Cytogenetic abnormalities are common in all species. The best data on incidence have been collected from humans, and that information seems to be very similar to what appears to be happening in other animals.

Incidence and Significance

Both the overall incidence, and the occurrence of specific abnormalities clearly depend upon when the data are collected relative to development.

This bias is clearly understood by considering the effect on survival of minor versus major genetic lesions. For example, when newborn children are screened, it is found that roughly 1 in every 200 has a chromosomal abnormality. Some of these children are phenotypically normal, while others have obvious, sometimes severe manifestations of disease. By definition however, these children have chromosomal disorders at the "mild" end of the spectrum because they are compatible with survival to term.

A much higher incidence of chromosomal disease is seen if one looks earlier in gestation. Approximately half of the human fetuses that are spontaneously aborted during the first trimester are chromosomally abnormal, reflecting chromosomal disorders severe enough to disrupt prenatal development.

If one looks at chromosomes in preimplantation embryos, even higher numbers of abnormalities are seen: 5-10% of viable blastocysts collected from cattle and pigs were cytogenetically abnormal. Finally, some chromosomal abnormalities are essentially never seen, presumably because they are so profound as to cause death shortly after fertilization.

The concepts on incidence presented above refer to the broad spectrum of chromosomal disorders. It is important to recognize that certain abnormalities can reach a very high and important prevalence in small populations of animals. This has been vividly observed with certain types of translocations, which reduce fertility yet cause little if any disease in carriers. A classic example is the 1/29 centric fusion in cattle, which has at times reached a prevalence of up to 30% in certain breeds within a particular country.

Causes of Chromosomal Disorders

Our understanding of the causes of chromosomal disorders is limited at best. Evidence has been presented to implicate such things as ionizing radiation, autoimmunity, virus infections and chemical toxins in the pathogenesis of certain disorders. It's easy to understand how, for example, radiation could break DNA and lead to deletions or, after rejoining of the DNA by cellular enzymes, such lesions as translocations.

Most cases of simple aneuploidy - monosomy or trisomy - are likely due to meiotic non-disjunctions. These are mistakes made in chromosome segregation during meiosis. If pairs of homologous chromosomes fail to separate during the first meiotic division or if the centromere joining sister chromatids fails to separate during the second meiotic division, gametes, and hence offspring, will be produced that have too many and too few chromosomes. These events are depicted in the following figure:

Disease Associations

What clinical presentation would lead you to suspect a chromosomal abnormality? Cytogenetic abnormalities have been identified in a diverse spectrum of disease states, particularly in humans. Moreover, chromosomal abnormalities are relatively common causes of specific types of disease. After ruling out more common causes in such cases, it is often warranted to perform a cytogenetic analysis.

  • Infertility and sterility in animals that have never been fertile is often the result of cytogenetic disease, particularly with regard to sex chromosome aneuploidy (e.g. XO, XXX, XXY genotypes). Cytogenetic analysis of such individuals is often warranted - if an abnormality is detected, further diagnostic efforts can be avoided.

  • Intersexes are animals in which genetic and phenotypic sex do not correspond (hermaphrodites and pseudohermaphrodites), and many have sex chromosome aneuploidy. Cytogenetic analysis of intersexes may be interesting, but, in animals, is rarely justified because the diagnosis that matters is already in hand.

  • Multiple congenital malformations are seen with many types of chromosomal abnormalities, particularly deletions and aneuploidy.

  • Mental retardation in humans is, in a few percent of cases, attributed to chromosomal disease. Well-known examples of this are Down and fragile X syndromes.

Back to the index of Cytogenetics

Last updated on December 8, 1996
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