Editing Germline mutation (section)

== Clinical implications ==
Different germline mutations can affect an individual differently depending on the rest of their genome. A [[Dominance (genetics)|dominant mutation]] only requires a single mutated gene to produce the disease [[phenotype]], while a recessive mutation requires both [[allele]]s to be mutated to produce the disease phenotype.<ref name=":11">{{cite web |url=http://genetics.thetech.org/about-genetics/mutations-and-disease |title=Mutations and Disease {{!}} Understanding Genetics |website=[[The Tech Interactive]] |archive-date=2021-09-14 |archive-url=https://web.archive.org/web/20210914101208/https://genetics.thetech.org/about-genetics/mutations-and-disease |url-status=dead}}</ref> For example, if the embryo inherits an already mutated allele from the father, and the same allele from the mother underwent an endogenous mutation, then the child will display the disease related to that mutated gene, even though only one parent carries the mutant allele.<ref name=":11" /> This is only one example of how a child can display a recessive disease while a mutant gene is only carried by one parent.<ref name=":11" /> Detection of chromosomal abnormalities can be found in utero for certain diseases by means of blood samples or ultrasound, as well as invasive procedures such as an [[amniocentesis]]. Later detection can be found by genome screening.

=== Cancer ===
Mutations in [[Tumor suppressor gene|tumour suppressor genes]] or [[proto-oncogenes]] can predispose an individual to developing tumors.<ref name=":10">{{Cite news|url=https://www.cancer.net/navigating-cancer-care/cancer-basics/genetics/genetics-cancer|title=The Genetics of Cancer|date=2012-03-26|work=Cancer.Net|access-date=2017-12-01}}</ref> It is estimated that inherited genetic mutations are involved in 5-10% of cancers.<ref name="genetics">{{cite web |title=The Genetics of Cancer |url=https://www.cancer.gov/about-cancer/causes-prevention/genetics |website=National Cancer Institute |publisher=NIH |access-date=23 September 2018|date=2015-04-22 }}</ref> These mutations make a person susceptible to tumor development if the other copy of the [[oncogene]] is randomly mutated. These mutations can occur in germ cells, allowing them to be [[Heritability|heritable]].<ref name=":10" /> Individuals who inherit germline mutations in [[TP53]] are predisposed to certain cancer variants because the protein produced by this gene suppresses tumors. Patients with this mutation are also at a risk for [[Li–Fraumeni syndrome]].<ref name="genetics" /> Other examples include mutations in the [[BRCA1]] and [[BRCA2]] genes which predispose to breast and ovarian cancer, or mutations in [[MLH1]] which predispose to [[hereditary nonpolyposis colorectal cancer|hereditary non-polyposis colorectal cancer]].

=== Huntington's disease ===
[[Huntington's disease]] is an [[autosomal dominant]] mutation in the HTT gene. The disorder causes degradation in the brain, resulting in uncontrollable movements and behavior.<ref name=":14">{{cite web |title=Huntington disease |url=https://ghr.nlm.nih.gov/condition/huntington-disease |website=Genetics Home Reference |publisher=NIH |access-date=23 September 2018}}</ref> The mutation involves an expansion of repeats in the Huntington protein, causing it to increase in size. Patients who have more than 40 repeats will most likely be affected. The onset of the disease is determined by the amount of repeats present in the mutation; the greater the number of repeats, the earlier symptoms of the disease will appear.<ref name=":14" /><ref>{{Cite book|title=Huntington's Disease|last=Lawrence|first=David M.|publisher=Infobase Publishing|year=2009|isbn=9780791095867|location=New York|pages=92}}</ref> Because of the dominant nature of the mutation, only one mutated allele is needed for the disease to be in effect. This means that if one parent is affected, the child will have a 50% chance of inheriting the disease.<ref name=":15">{{cite web |title=Huntington's disease |url=https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/symptoms-causes/syc-20356117 |website=Mayo Clinic |access-date=23 September 2018}}</ref> This disease does not have carriers because if a patient has one mutation, they will (most likely) be affected. The disease typically has a late onset, so many parents have children before they know they have the mutation. The HTT mutation can be detected through [[Genetic testing|genome screening]].

=== Trisomy 21 ===
Trisomy 21 (also known as [[Down syndrome]]) results from a child having three copies of chromosome 21.<ref name=":3" /> This chromosome duplication occurs during germ cell formation, when both copies of chromosome 21 end up in the same [[Cell division|daughter cell]] in either the mother or father, and this mutant germ cell participates in fertilization of the zygote.<ref name=":3">{{cite journal | vauthors = Chandley AC | title = On the parental origin of de novo mutation in man | journal = Journal of Medical Genetics | volume = 28 | issue = 4 | pages = 217–23 | date = April 1991 | pmid = 1677423 | doi = 10.1136/jmg.28.4.217 | pmc=1016821}}</ref> Another, more common way this can occur is during the first cell division event after the formation of the zygote.<ref name=":3" /> The risk of Trisomy 21 increases with maternal age with the risk being 1/2000 (0.05%) at age 20 increasing to 1/100 (1%) at age 40.<ref>{{cite journal |last1=Hook |first1=EB |title=Rates of chromosome abnormalities at different maternal ages |journal=Obstetrics and Gynecology | date = September 1981 |volume=27 |issue=1 |pages=282–5 |doi=10.1016/0091-2182(82)90145-8 |pmid=6455611 }}</ref> This disease can be detected by non-invasive as well as invasive procedures prenatally. Non-invasive procedures include scanning for [[fetal DNA]] through maternal plasma via a blood sample.<ref>{{cite journal |last1=Ghanta |first1=Sujana |title=Non-Invasive Prenatal Detection of Trisomy 21 Using Tandem Single Nucleotide Polymorphisms |journal=PLOS ONE | date = October 2010 |volume=5 |issue=10 |pages=e13184 |doi=10.1371/journal.pone.0013184 |pmid=20949031 |pmc=2951898 |bibcode=2010PLoSO...513184G |doi-access=free }}</ref>

=== Cystic fibrosis ===
Cystic fibrosis is an [[Dominance (genetics)|autosomal recessive]] disorder that causes a variety of symptoms and complications, the most common of which is a thick mucous lining in lung [[Epithelium|epithelial]] tissue due to improper salt exchange, but can also affect the [[pancreas]], [[Gastrointestinal tract|intestines]], [[liver]], and [[kidney]]s.<ref name=":4">{{cite web|url=http://www.cysticfibrosis.ca/about-cf|title=Cystic Fibrosis Canada|website=www.cysticfibrosis.ca|access-date=2017-11-30}}</ref><ref>{{cite journal | vauthors = O'Sullivan BP, Freedman SD | title = Cystic fibrosis | journal = Lancet | volume = 373 | issue = 9678 | pages = 1891–904 | date = May 2009 | pmid = 19403164 | doi = 10.1016/S0140-6736(09)60327-5 | s2cid = 46011502 }}</ref> Many bodily processes can be affected due to the hereditary nature of this disease; if the disease is present in the DNA of both the sperm and the egg, then it will be present in essentially every cell and organ in the body; these mutations can occur initially in the germline cells, or be present in all parental cells.<ref name=":4" /> The most common mutation seen in this disease is ΔF508, which means a deletion of the amino acid at the 508 position.<ref>{{cite web|url=https://ghr.nlm.nih.gov/gene/CFTR#conditions|title=CFTR gene|last=Reference|first=Genetics Home|website=Genetics Home Reference|access-date=2017-11-30}}</ref> If both parents have a mutated [[Cystic fibrosis transmembrane conductance regulator|CFTR]] (cystic fibrosis transmembrane conductance regulator) protein, then their children have a 25% of inheriting the disease.<ref name=":4" /> If a child has one mutated copy of CFTR, they will not develop the disease, but will become a carrier of the disease.<ref name=":4" /> The mutation can be detected before birth through amniocentesis, or after birth via prenatal genetic screening.<ref name=":16">{{cite web |title=Prenatal Diagnosis |url=https://www.hopkinscf.org/what-is-cf/diagnosis/presentations/prenatal-diagnosis/ |website=Johns Hopkins Cystic Fibrosis Center |access-date=23 September 2018}}</ref>