Multifactorial inheritance

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:

• Diabetes Mellitus
• Cancer
• Cleft palate
• Club foot

Multifactorially inherited diseases are said to constitute the majority of all genetic disorders affecting humans which will result in hospitalization or special care of some kind .

Multifactorial traits in general

Generally, multifactorial traits outside of illness contribute to what we see as continuous characteristics in organisms, such as height, skin colour, and body mass. All of these phenotypes are complicated by a great deal of interplay between genes and environment. While some authors include intelligence in the same vein, and it is tempting to do so, the problem with intelligence is that it is so ill-defined. Indeed, the Wikipedia entry on intelligence offers so many definitions, that the point is easily made that there is no definable entity called intelligence that one could say amounts to a definable cluster of heritable traits.

Due to the nature of multifactorial traits, inheritance will not follow the same pattern as a simple monohybrid or dihybrid cross. Multifactorial, or polygenic inheritance can be explained as Mendelian inheritance at many loci.

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 with or without 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. This shows that multifactorial inheritance is polygenic, and genetic frequencies can be predicted by way of a polyhybrid Mendelian cross. Phenotypic frequencies are a different matter, especially if they are complicated by environmental factors.

The paradigm of polygenic inheritance as being used to define multifactorial disease has encountered much disagreement. Turnpenny, Peter discusses how simple polygenic inheritance cannot explain the onset of diabetes mellitus, and that in cases such as these, not all genes are thought to make an equal contribution.

The assumption of polygenic inheritance is that all involved loci make an equal contribution to the symptoms of the disease. This should result in a normal curve distribution of genotypes. When it does not, then idea of polygenetic inheritance cannot be supported for that illness.

A cursory look at some examples

Examples of such diseases are not new to medicine. The above examples are well-known examples of diseases having both genetic and environmental components. Other examples involve atopic diseases such as eczema or dermatitis; also spina bifida (open spine) and anencephaly (open skull) are other examples.

While schizophrenia is widely believed to be multifactorially genetic by biopsychiatrists, no characteristic genetic markers have been determined with any certainty.

Is it multifactorially heritable?

It is difficult to ascertain if any particular disease is multifactorially genetic. If a pedigree chart is taken of the patient's family and relations, and it is shown that the brothers and sisters of the patient have a multifactorially inherited disease, then there is a strong chance that the patient will also be a genetic carrier. This likelihood is reduced if only cousins and more distant relatives have the disease. It must be stated that while multifactorially-inherited disease tends to run in families, inheritance will not follow the same pattern as a simple monohybrid or dihybrid cross.

If a genetic cause is suspected and little else is known about the illness, then 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 determine 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.