It has been known since biblical times that some diseases tend to cluster within families, and apparently occur more commonly within groups of blood relatives. The mechanisms of human genetics have gradually been discovered over the last century, and an understanding of these mechanisms is now able to explain many aspects of inherited human disease, and of the normal diversity between individuals.
Genetic diseases fall into one of three categories:
hromosomal disorders involve the lack, excess or abnormal arrangement of one or more chromosomes, producing large amounts of excessive or deficient genetic material, and normally affecting many different genes. It is also possible for a single individual to show chromosomal mosaicism, in which more than one pattern of chromosomal constitution is present in various different cell lines of their body. Chromosomal abnormalities may affect the 22 pairs of autosomes, or the 2 sex chromosomes.
The most common of the autosomal abnormalities in liveborn infants is Trisomy 21 (Down syndrome). For reasons that are not well understood as yet, chromosomal aberrations also occur with high frequency in various malignancies.
Monogenic (or Mendelian) disorders are determined primarily by a single mutant gene. These disorders display simple (Mendelian) inheritance patterns that can be classified into autosomal dominant, autosomal recessive, or X-linked types.
Examples of monogenic disorders include:
Within certain population groups, some monogenic disorders may be extremely common: sickle-cell anaemia has high incidence amongst US blacks, cystic fibrosis amongst Northern European Caucasians and Tay-Sachs disease amongst Ashkenazi Jews. Multifactorial genetic disorders are caused by an interaction of multiple genes with various factors in the external environment of the cell or the individual.
Any of multiple independent genes may predispose or increase the risk of an individual to having a multifactorial disease, but this risk may only be realised if that individual is exposed to certain environmental factors or stimuli during life. For example, some forms of hypertension, atherosclerotic heart disease and diabetes mellitus may involve complex interactions between multiple genetic factors, diet, lifestyle and environment.
Long standing controversies have existed within the profession about the significance of genetic vs acquired traits. For example, sexuality (is homosexuality genetic or environmental?), intelligence (nature/nurture), some social behaviours (Eysenk's twin studies).
Gelehrter TD. 1998. Principles of Medical Genetics. (2nd Ed.) ISBN 0683034456
opac.library.usyd.edu.au/record=b2310731~S4
Scriver CR, Sly WS, Childs B, Beaudet AL, Valle D, Kinzler KW, Vogelstein B eds. 2000. The Metabolic and Molecular Bases of Inherited Disease. (8th Ed.) New York: McGraw-Hill, ISBN 0079130356 (4-volume set)
opac.library.usyd.edu.au/record=b2436991~S4
E-Book 2002 at:
opac.library.usyd.edu.au/record=b2773371~S4
Connor JM, Ferguson-Smith MA. 1997. Essential Medical Genetics. (5th Ed.) Oxford: Blackwell Scientific, ISBN 086542666X
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McKusick VA. 1998. Mendelian Inheritance in Man. (12th Ed.) Baltimore: John Hopkins University Press, ISBN 0801857422 (3-volume set)
opac.library.usyd.edu.au/record=b2294058~S4
The Online Mendelian Inheritance in Man is a valuable reference.