Editing Quantitative trait locus (section)

==Quantitative traits==
{{See also|Monogenic inheritance|Oligogenic inheritance}}
'''Polygenic inheritance''' refers to inheritance of a [[phenotype|phenotypic]] characteristic (trait) that is attributable to two or more [[genes]] and can be measured quantitatively. '''Multifactorial inheritance''' refers to polygenic inheritance that also includes interactions with the environment. Unlike [[monogenic trait]]s, polygenic traits do not follow patterns of [[Mendelian inheritance]] (discrete categories). Instead, their phenotypes typically vary along a continuous gradient depicted by a [[Normal distribution|bell curve]].<ref>{{
citation
|author=Ricki Lewis
|title=Multifactorial Traits
|url=http://highered.mcgraw-hill.com/sites/007246268x/student_view0/chapter7/
|publisher=McGraw-Hill Higher Education
|date=2003
}}.</ref>

An example of a polygenic trait is [[human skin color]] variation. Several genes factor into determining a person's natural skin color, so modifying only one of those genes can change skin color slightly or in some cases, such as for [[SLC24A5]], moderately. Many disorders with [[genetic disorder|genetic components]] are polygenic, including [[autism]], [[cancer]], [[diabetes]] and numerous others. Most phenotypic characteristics are the result of the interaction of multiple genes.{{cn|date=July 2024}}


Multifactorially inherited diseases are said to constitute the majority of genetic disorders affecting humans which will result in hospitalization or special care of some kind.<ref name="Tissot">
{{cite web  | last = Tissot  | first = Robert  | title = Human Genetics for 1st Year Students: Multifactorial Inheritance  | url = http://www.uic.edu/classes/bms/bms655/lesson11.html  | access-date = 6 January 2007 }}
</ref><ref name="Clinical Genetics">
{{cite web  |author=Birth Defects Genetics Centre, University of South Dakota School of Medicine  | title = Multifactorial Inheritance  | work = Clinical Genetics: A Self-Study Guide for Health Care Providers  | publisher = University of South Dakota School of Medicine  | url = http://www.usd.edu/med/som/genetics/curriculum/1GMULTI5.htm  | access-date = 6 January 2007 |archive-url = https://web.archive.org/web/20061230084542/http://www.usd.edu/med/som/genetics/curriculum/1GMULTI5.htm |archive-date = 30 December 2006}}
</ref>

===Multifactorial traits in general===
Traits controlled both by the environment and by genetic factors are called multifactorial.
Usually, multifactorial traits outside of illness result in what we see as '''continuous characteristics''' in organisms, especially human organisms such as: height,<ref name="Tissot" /> skin color, and body mass.<ref name="MedicineNet">{{cite web  | title = Definition of Multifactorial inheritance  | work = MedicineNet.com MedTerms Dictionary  | publisher = MedicineNet.com  | url = http://www.medterms.com/script/main/art.asp?articlekey=4453  | access-date = 6 January 2007  | archive-date = 17 December 2013  | archive-url = https://web.archive.org/web/20131217193339/http://www.medterms.com/script/main/art.asp?articlekey=4453  | url-status = dead  }}</ref> All of these phenotypes are complicated by a great deal of give-and-take between genes and environmental effects.<ref name="Tissot" /> The continuous distribution of traits such as height and skin color described above, reflects the action of genes that do not manifest typical patterns of dominance and recessiveness. Instead the contributions of each involved locus are thought to be additive. Writers have distinguished this kind of inheritance as ''polygenic'', or ''quantitative inheritance''.<ref name="Turnpenny">
{{cite book  | last = Turnpenny  | first = Peter  | title = Emery's Elements of Medical Genetics  | edition = 12th  | chapter = Chapter 9  | publisher = Elsevier  | date = 2004  | chapter-url = http://www.fleshandbones.com/readingroom/viewchapter.cfm?ID=1041  | chapter-format = PDF  | access-date = 6 January 2007 }}
</ref>

Thus, due to the nature of polygenic traits, inheritance will not follow the same pattern as a simple [[monohybrid cross|monohybrid]] or [[dihybrid cross]].<ref name="Clinical Genetics" /> Polygenic inheritance can be explained as Mendelian inheritance at many loci,<ref name="Tissot" /> resulting in a trait which is [[normal distribution|normally-distributed]]. If ''n'' is the number of involved loci, then the coefficients of the [[binomial distribution|binomial expansion]] of (''a'' + ''b'')<sup>''2n''</sup> will give the frequency of distribution of all ''n'' allele [[combination]]s. For sufficiently high values of ''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 threshold value. Disease states of increasing severity will be expected the further one goes past the threshold and away from the [[statistical mean|mean]].<ref name="Turnpenny" />

===Heritable disease and multifactorial inheritance===
A mutation resulting in a disease state is often recessive, so both alleles must be mutant in order for the disease to be expressed phenotypically. A disease or syndrome may also be the result of the expression of mutant alleles at more than one locus. 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.{{cn|date=July 2024}}

The more genes involved in the cross, the more the distribution of the [[genotype]]s will resemble a [[normal distribution|normal, or Gaussian]] distribution.<ref name="Tissot" /> This shows that multifactorial inheritance is polygenic, and genetic frequencies can be predicted by way of a polyhybrid [[Mendelian inheritance|Mendelian]] cross. Phenotypic frequencies are a different matter, especially if they are complicated by environmental factors.{{cn|date=July 2024}}

The paradigm of polygenic inheritance as being used to define multifactorial disease has encountered much disagreement. Turnpenny (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.<ref name="Turnpenny" />

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 (Gaussian) distribution of genotypes. When it does not, the idea of polygenetic inheritance cannot be supported for that illness.{{cn|date=July 2024}}

===Examples===
The above are well-known examples of diseases having both genetic and environmental components. Other examples involve atopic diseases such as [[atopic eczema|eczema]] or [[atopic dermatitis|dermatitis]],<ref name="Tissot"/> [[spina bifida]] (open spine), and [[anencephaly]] (open skull).<ref name="Proud">{{cite web  | author = Proud, Virginia  | author2 = Roberts, Helen  | name-list-style = amp  | title = Medical Genetics: Multifactorial Inheritance  | publisher = Children's Hospital of the King's Daughters  | date = 31 December 2005  | url = http://www.chkd.org/HealthLibrary/Content.aspx?pageid=P02134  | access-date = 6 January 2007  | archive-date = 15 October 2006  | archive-url = https://web.archive.org/web/20061015185017/http://www.chkd.org/HealthLibrary/Content.aspx?pageid=P02134  | url-status = dead  }}</ref>

While [[schizophrenia]] is widely believed to be multifactorially genetic by [[Biopsychiatry|biopsychiatrists]], no characteristic genetic markers have been determined with any certainty.{{cn|date=July 2024}}

If 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{{citation needed|date=March 2017}} and that the patient will also be a genetic carrier. This is not quite enough as 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.{{cn|date=July 2024}}

If multifactorial inheritance is indeed the case, then the chance of the patient contracting the disease is reduced only if cousins and more distant relatives have the disease.<ref name="Proud" /> While multifactorially-inherited diseases tend to run in families, inheritance will not follow the same pattern as a simple [[monohybrid cross|monohybrid]] or [[dihybrid cross]].<ref name="Clinical Genetics" />

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 are there differences in expression between them? 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, this is not usually the first avenue of investigation one would choose to determine etiology.{{citation needed|date=August 2017}}

[[File:Example of QTL-Scan on a single Chromosom from PLoS Biology.jpg|thumb|right|A QTL for [[osteoporosis]] on the human chromosome 20]]