Editing Phenylketonuria (section)

==Genetics==
[[Image:autorecessive.svg|thumb|250px|Phenylketonuria is inherited in an [[Dominance (genetics)|autosomal recessive]] fashion.]]

PKU is an [[Dominance (genetics)|autosomal recessive]] metabolic [[genetic disorder]]. As such, two PKU [[allele]]s are required for an individual to experience symptoms of the disease. For a child to inherit PKU, both parents must have and pass on the defective gene.<ref>{{Cite web |title=Phenylketonuria (PKU) - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/phenylketonuria/symptoms-causes/syc-20376302 |access-date=2020-03-10 |website=Mayo Clinic |language=en}}</ref> If both parents are carriers for PKU, any child they have will have a 25% chance to be born with the disorder, a 50% chance the child will be a carrier, and a 25% chance the child will neither develop nor be a carrier for the disease.<ref name=NIH2000/> 

PKU is characterized by [[homozygous]] or [[compound heterozygosity|compound heterozygous]] [[mutation]]s in the gene for the hepatic enzyme [[phenylalanine hydroxylase]] (PAH), rendering it nonfunctional.<ref name="Andrews">{{Cite book |last1=James |first1=William D. |title=Andrews' Diseases of the Skin: clinical Dermatology |last2=Berger |first2=Timothy G. |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6}}</ref>{{Rp|541}} This enzyme is necessary to metabolize the amino acid [[phenylalanine]] (Phe) to the amino acid [[tyrosine]]. When PAH activity is reduced, Phe accumulates and is converted into [[phenylpyruvate]] (also known as phenylketone), which can be detected in the [[urine]].<ref name="Gonzalez, Jason; Willis, Monte S. 118–119">{{Cite journal |last1=Gonzalez |first1=Jason |last2=Willis |first2=Monte S. |date=Feb 2010 |title=Ivar Asbjörn Følling |journal=Laboratory Medicine |volume=41 |issue=2 |pages=118–119 |doi=10.1309/LM62LVV5OSLUJOQF |doi-access=free}}</ref>

Carriers of a single PKU allele do not exhibit symptoms of the disease, but appear to be protected to some extent against the fungal toxin [[ochratoxin A]]. [[Louis Isaac Woolf|Louis Woolf]] suggested that this accounted for the persistence of the allele in certain populations,<ref name="Woolf">{{Cite journal |author-link=Louis Isaac Woolf |vauthors=Woolf LI |date=May 1986 |title=The heterozygote advantage in phenylketonuria |journal=American Journal of Human Genetics |volume=38 |issue=5 |pages=773–5 |pmc=1684820 |pmid=3717163}}</ref> in that it confers a [[fitness (biology)|selective advantage]]—in other words, being a [[Heterozygote advantage|heterozygote is advantageous]].<ref name="Lewis1997">{{Cite book |last=Lewis |first=Ricki |title=Human Genetics |date=1997 |publisher=Wm. C. Brown |isbn=978-0-697-24030-9 |location=Chicago, IL |pages=247–248}}</ref>

The gene for PAH is located on [[chromosome 12 (human)|chromosome 12]] in the bands 12q22-q24.2.<ref>{{Cite book |last1=Rosenberg |first1=Roger N. |url=https://books.google.com/books?id=p3i0BdSlpukC&pg=PA820 |title=The Molecular and Genetic Basis of Neurologic and Psychiatric Disease |last2=Barchi |first2=Robert L. |author-link2=Robert L. Barchi |last3=DiMauro |first3=Salvatore |author-link3=Salvatore DiMauro |last4=Prusiner |first4=Stanley B. |author-link4=Stanley B. Prusiner |last5=Nestler |first5=Eric J. |author-link5=Eric J. Nestler |date=2003 |publisher=Butterworth-Heinemann |isbn=9780750673600 |page=820 |language=en}}</ref> As of 2000, around 400 disease-causing mutations had been found in the ''PAH'' gene. This is an example of allelic [[genetic heterogeneity]].<ref name=NIH2000/>