Editing Point mutation (section)

==Specific diseases caused by point mutations==
===Cancer===
Point mutations in multiple tumor suppressor proteins cause [[cancer]]. For instance, point mutations in Adenomatous Polyposis Coli promote tumorigenesis.<ref name="APC point mutations">{{cite journal |vauthors=Minde DP, Anvarian Z, Rüdiger SG, Maurice MM |title=Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? |journal=Mol. Cancer |volume=10 |pages=101 |year=2011 |pmid=21859464 |pmc=3170638 |doi=10.1186/1476-4598-10-101 |doi-access=free }}</ref> A novel assay, [[Fast parallel proteolysis (FASTpp)]], might help swift screening of specific stability defects in individual cancer patients.<ref>{{cite journal |vauthors=Minde DP, Maurice MM, Rüdiger SG |title=Determining biophysical protein stability in lysates by a fast proteolysis assay, FASTpp |journal=PLOS ONE |volume=7 |issue=10 |pages=e46147 |year=2012 |pmid=23056252 |pmc=3463568 |doi=10.1371/journal.pone.0046147 |bibcode=2012PLoSO...746147M |doi-access=free }}</ref>

===Neurofibromatosis===

[[Neurofibromatosis]] is caused by point mutations in the [[Neurofibromin 1]]<ref name="pmid11409870">{{Cite journal
 | pmid = 11409870
| doi = 10.1007/s004390100514
| year = 2001
| last1 = Serra
| first1 = E
| title = Somatic NF1 mutational spectrum in benign neurofibromas: MRNA splice defects are common among point mutations
| journal = Human Genetics
| volume = 108
| issue = 5
| pages = 416–29
| last2 = Ars
| first2 = E
| last3 = Ravella
| first3 = A
| last4 = Sánchez
| first4 = A
| last5 = Puig
| first5 = S
| last6 = Rosenbaum
| first6 = T
| last7 = Estivill
| first7 = X
| last8 = Lázaro
| first8 = C
| s2cid = 2136834
}}</ref><ref name="pmid14635100">{{Cite journal
 | pmid = 14635100
| year = 2003
| last1 = Wiest
| first1 = V
| title = Somatic NF1 mutation spectra in a family with neurofibromatosis type 1: Toward a theory of genetic modifiers
| journal = Human Mutation
| volume = 22
| issue = 6
| pages = 423–7
| last2 = Eisenbarth
| first2 = I
| last3 = Schmegner
| first3 = C
| last4 = Krone
| first4 = W
| last5 = Assum
| first5 = G
| doi = 10.1002/humu.10272
| s2cid = 22140210
| doi-access = free
}}</ref> or [[Neurofibromin 2]] gene.<ref name="pmid12011146">{{Cite journal
 | pmid = 12011146
| pmc = 1735110
| year = 2002
| last1 = Mohyuddin
| first1 = A
| title = Molecular genetic analysis of the NF2 gene in young patients with unilateral vestibular schwannomas
| journal = Journal of Medical Genetics
| volume = 39
| issue = 5
| pages = 315–22
| last2 = Neary
| first2 = W. J.
| last3 = Wallace
| first3 = A
| last4 = Wu
| first4 = C. L.
| last5 = Purcell
| first5 = S
| last6 = Reid
| first6 = H
| last7 = Ramsden
| first7 = R. T.
| last8 = Read
| first8 = A
| last9 = Black
| first9 = G
| last10 = Evans
| first10 = D. G.
 | doi=10.1136/jmg.39.5.315
}}</ref>

===Sickle-cell anemia===
[[Sickle-cell anemia]] is caused by a point mutation in the β-globin chain of hemoglobin, causing the hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position.

The β-globin gene is found on the short arm of chromosome 11. The association of two wild-type α-globin subunits with two mutant β-globin subunits forms hemoglobin S (HbS). Under low-oxygen conditions (being at high altitude, for example), the absence of a polar amino acid at position six of the β-globin chain promotes the non-covalent polymerisation (aggregation) of hemoglobin, which distorts red blood cells into a sickle shape and decreases their elasticity.<ref>{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK22183/|title=Genes and Disease|first=<!-- National Center for Biotechnology Information -->|last=<!-- (US) -->|date=29 September 1998|publisher=National Center for Biotechnology Information (US)|via=PubMed}}</ref>

[[Hemoglobin]] is a protein found in red blood cells, and is responsible for the transportation of oxygen through the body.<ref>{{cite journal |author=Hsia CC |title=Respiratory function of hemoglobin |journal=N. Engl. J. Med. |volume=338 |issue=4 |pages=239–47 |date=January 1998 |pmid=9435331 |doi=10.1056/NEJM199801223380407 }}</ref> There are two subunits that make up the hemoglobin protein: [[HBB|beta-globins]] and [[hemoglobin, alpha 1|alpha-globins]].<ref>{{cite web |title=HBB — Hemoglobin, Beta |work=Genetics Home Reference |publisher=National Library of Medicine |url=http://ghr.nlm.nih.gov/gene/HBB}}</ref>
Beta-hemoglobin is created from the genetic information on the HBB, or "hemoglobin, beta" gene found on chromosome 11p15.5.<ref name=NBK22238>{{cite book |chapter=Anemia, Sickle Cell |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK22238/ |title=Genes and Disease |publisher=National Center for Biotechnology Information |location=Bethesda MD |year=1998 |id=NBK22183 |url=https://www.ncbi.nlm.nih.gov/books/NBK22183/}}</ref>  A single point mutation in this polypeptide chain, which is 147 amino acids long, results in the disease known as Sickle Cell Anemia.<ref name="nature1">{{cite journal |author=Clancy S |title=Genetic Mutation |journal=Nature Education |volume=1 |issue=1 |pages=187 |year=2008 |url=http://www.nature.com/scitable/topicpage/genetic-mutation-441}}</ref>
Sickle-cell anemia is an autosomal recessive disorder that affects 1 in 500 African Americans, and is one of the most common blood disorders in the United States.<ref name=NBK22238/>  The single replacement of the sixth amino acid in the beta-globin, glutamic acid, with valine results in deformed red blood cells.  These sickle-shaped cells cannot carry nearly as much oxygen as normal red blood cells and they get caught more easily in the capillaries, cutting off blood supply to vital organs.  The single nucleotide change in the beta-globin means that even the smallest of exertions on the part of the carrier results in severe pain and even heart attack.  Below is a chart depicting the first thirteen amino acids in the normal and abnormal [[sickle cell]] polypeptide chain.<ref name="nature1"/>

{| class="wikitable"
|+Sequence for normal hemoglobin
|-
| AUG || GUG || CAC || CUG || ACU || CCU || G<span style="color:red">A</span>G || GAG || AAG || UCU || GCC || GUU || ACU
|-
| START || [[Valine|Val]] || [[Histidine|His]] || [[Leucine|Leu]] || [[Threonine|Thr]] || [[Proline|Pro]] || [[Glutamic Acid|<span style="color:red">Glu</span>]] || [[Glutamic Acid|Glu]] || [[Lysine|Lys]] || [[Serine|Ser]] || [[Alanine|Ala]] || [[Valine|Val]] || [[Threonine|Thr]]
|}

{| class="wikitable"
|+ Sequence for sickle-cell hemoglobin
|-
| AUG || GUG || CAC || CUG || ACU || CCU || G<span style="color:red">U</span>G || GAG || AAG || UCU || GCC || GUU || ACU
|-
| START || [[Valine|Val]] || [[Histidine|His]] || [[Leucine|Leu]] || [[Threonine|Thr]] || [[Proline|Pro]] || [[Valine|<span style="color:red">Val</span>]] || [[Glutamic Acid|Glu]] || [[Lysine|Lys]] || [[Serine|Ser]] || [[Alanine|Ala]] || [[Valine|Val]] || [[Threonine|Thr]]
|}

===Tay–Sachs disease===
The cause of [[Tay–Sachs disease]] is a genetic defect that is passed from parent to child. This genetic defect is located in the HEXA gene, which is found on chromosome 15.

The HEXA gene makes part of an enzyme called beta-hexosaminidase A, which plays a critical role in the nervous system. This enzyme helps break down a fatty substance called GM2 ganglioside in nerve cells.
Mutations in the HEXA gene disrupt the activity of beta-hexosaminidase A, preventing the breakdown of the fatty substances. As a result, the fatty substances accumulate to deadly levels in the brain and spinal cord.  The buildup of GM2 ganglioside causes progressive damage to the nerve cells.  This is the cause of the signs and symptoms of Tay-Sachs disease.<ref>{{cite web|url=http://nervous-system.emedtv.com/tay-sachs-disease/causes-of-tay-sachs.html|title=Causes of Tay-Sachs|last=eMedTV|access-date=28 December 2011|archive-date=6 August 2020|archive-url=https://web.archive.org/web/20200806104952/http://nervous-system.emedtv.com/tay-sachs-disease/causes-of-tay-sachs.html|url-status=dead}}</ref>