Multifactorial inheritance
Introduction
In epidemiological terminology, multifactorial inheritance, alternately known as polygenic inheritance or quantitative inheritance describes a pattern of predisposition for a disease process which is the result of multiple genetic alterations (mutations) , which may or may not be combined with multiple environmental factors.
Examples of disease processes generally considered to be results of multifactorial etiology:
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[7] [8].
Multifactorial traits in general
Generally, multifactorial traits outside of illness contribute to what we see as continuous characteristics in organisms, such as height[9], skin colour, and body mass[10]. All of these phenotypes are complicated by a great deal of interplay between genes and environment[11]. While some authors[12] [13] 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 single, agreed-upon entity called intelligence that one could say amounts to a definable cluster of heritable traits. [citation needed]
The continuous distribution of traits such as height and skin colour described above reflects the action of genes that do not quite show typical patterns of dominance and recessiveness. Instead the contributions of each involved loci are thought to be additive. Writers have distinguished this kind of inheritance as polygenic, or quantitative inheritance[14].
Thus, due to the nature of polygenic traits, inheritance will not follow the same pattern as a simple monohybrid or dihybrid cross[15]. Polygenic inheritance can be explained as Mendelian inheritance at many loci[16], resulting in a trait which is normally-distributed. If n is the number of involved loci, then the coefficients of the binomial expansion of (a + b)2n will give the frequency of distribution of all n allele combinations. For a sufficiently high n, this binomial distribution will begin to resemble a normal distribution. From this viewpoint, a disease state will become apparent at one of the tails of the distribution, past some threshhold value. Disease states of increasing severity will be expected the further one goes past the threshhold and away from the mean[17].
There are, however, many traits and disease states where many genes are involved, but their contribution is not equal, or additive.
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 presence 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[18]. 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 (2004) discusses how simple polygenic inheritance cannot explain some diseases such as the onset of Type I diabetes mellitus, and that in cases such as these, not all genes are thought to make an equal contribution[19].
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[20]; also spina bifida (open spine) and anencephaly (open skull) are other examples[21].
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 the disease, then there is a strong chance that the disease is genetic and that the patient will also be a genetic carrier. But this is not quite enough. It also needs to be proven that the pattern of inheritance is non-Mendelian. This would require studying dozens, even hundreds of different family pedigrees before a conclusion of multifactorial inheritance is drawn. This often takes several years.
If multifactorial inheritance is indeed the case, then the chance of the patient contracting the disease is reduced if only cousins and more distant relatives have the disease[22]. 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[23].
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. Due to the involved nature of genetic investigations needed to determine such inheritance patterns, is not usually the first avenue of investigation one would choose to determine etiology.
Psychiatry has determined, often without sufficient evidence, that mental illness follows this pattern. The problem with mental illness itself is that most diagnoses is largely subjective, and even the nosologies in DSM-IV are not widely agreed upon. The example most often cited as an example of a multifactorial mental illness is schizophrenia, however, no genes have been isolated to date. It has been said that genetic causes of mental illness is being emphasised at the expense of paying sufficient attention to environmental factors, especially in the field of biopsychiatry. [citation needed]
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.
References
- ^ "Multifactorial Inheritance". Pregnancy and Newborn Health Education Centre. The March of Dimes. Retrieved 6 Jan 2007.
- ^ "Multifactorial Inheritance". Pregnancy and Newborn Health Education Centre. The March of Dimes. Retrieved 6 Jan 2007.
- ^
"Medical Genetics: Multifactorial Inheritance". Children's Hospital of the King's Daughters. 31 December 2005. Retrieved 6 Jan 2006.
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"Medical Genetics: Multifactorial Inheritance". Children's Hospital of the King's Daughters. 31 December 2005. Retrieved 6 Jan 2006.
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- ^ Tissot, Robert. "Human Genetics for 1st Year Students: Multifactorial Inheritance". Retrieved 6 Jan 2007.
- ^
"Multifactorial Inheritance". Clinical Genetics: A Self-Study Guide for Health Care Providers. University of South Dakota School of Medicine. Retrieved 6 Jan 2007.
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- ^ "Definition of Multifactorial inheritance". MedicineNet.com MedTerms Dictionary. MedicineNet.com. Retrieved 6 January 2007.
- ^ Tissot, Robert. "Human Genetics for 1st Year Students: Multifactorial Inheritance". Retrieved 6 Jan 2007.
- ^ Tissot, Robert. "Human Genetics for 1st Year Students: Multifactorial Inheritance". Retrieved 6 Jan 2007.
- ^ "Definition of Multifactorial inheritance". MedicineNet.com MedTerms Dictionary. MedicineNet.com. Retrieved 6 January 2007.
- ^ Turnpenny, Peter (2004). "Emery's Elements of Medical Genetics, 12th Edition, Chapter 9" (PDF). Elsevier. Retrieved 6 January 2007.
- ^
"Multifactorial Inheritance". Clinical Genetics: A Self-Study Guide for Health Care Providers. University of South Dakota School of Medicine. Retrieved 6 Jan 2007.
{{cite web}}
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- ^ Turnpenny, Peter (2004). "Emery's Elements of Medical Genetics, 12th Edition, Chapter 9" (PDF). Elsevier. Retrieved 6 January 2007.
- ^ http://www.uic.edu/classes/bms/bms655/lesson11.html
- ^ Turnpenny, Peter (2004). "Emery's Elements of Medical Genetics, 12th Edition, Chapter 9" (PDF). Elsevier. Retrieved 6 January 2007.
- ^ http://www.uic.edu/classes/bms/bms655/lesson11.html
- ^
"Medical Genetics: Multifactorial Inheritance". Children's Hospital of the King's Daughters. 31 December 2005. Retrieved 6 Jan 2006.
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"Medical Genetics: Multifactorial Inheritance". Children's Hospital of the King's Daughters. 31 December 2005. Retrieved 6 Jan 2006.
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"Multifactorial Inheritance". Clinical Genetics: A Self-Study Guide for Health Care Providers. University of South Dakota School of Medicine. Retrieved 6 Jan 2007.
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