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Multifactorial inheritance

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Introduction

In epidemiological terminology, multifactorial inheritance, alternately known as polygenic inheritance describes a pattern of predisposition for a disease process which is the result of multiple genetic alterations (mutations) , multiple environmental factors, or a combination of one or more of these two.

Examples of disease processes generally considered to be results of multifactorial etiology:

Heritable disease and multifactorial inheritance

The carrier gene of a disease which can be passed on to offspring is usually recessive; rarely dominant. The phenotypic expression of the disease or syndrome may even be the result of one or more genes being expressed together. When more than one gene is involved in the prescence of environmental triggers, we say that the disease is the result of multifactorial inheritance.

The more genes involved in the cross, the more the distribution of the genotypes will resemble a normal, or Gaussian distribution[1].

A cursory look at the above examples

Examples of such diseases are not new to medicine. Atherosclerosis (hardening of the arteries), osteoporosis (softening of bones due to loss of calcium) are well-known examples of diseases having both genetic and environmental components. While schizophrenia is widely believed to be multifactorially genetic by biopsychiatrists, no characteristic genetic markers have been determined with any certainty. Oral cancer, or cancer in general, is the result of mutagens triggering mutations whcih activate oncogenes. The result is an uncontrolled replication of cells; mitosis gone out of control. Oral cancer, like in all cancers, are not heritable, but genes are the vehicle exploited by mutagens to express the disease.

Is it multifactorially heritable?

It is difficult to ascertain if any particular disease is multifactorially genetic. This is because such diseases do not show up clearly on a pedigree chart (except possibly to determine high or low frequency); and even if a genetic cause is suspected, it remains to be seen exactly how many genes are involved in the phenotypic expression of the disease. Once that is determined, the question must be answered: if two people have the required genes, why some people still don't express the disease. Generally, what makes the two individuals different are likely to be environmental factors. Overall, such investigations are difficult and arduous to carry out, sometimes taking several years to reach any conclusions. It is not usually the first avenue of investigation one would choose to find etiology.

More often than not, investigators will hypothesise that a disease is multifactorially heritable, along with a cluster of other hypotheses when it is not known what causes the disease.