Editing Human variability (section)

===Measuring genetic variation===
[[Human Genome|Human genomics]] and [[population genetics]] are the study of the human genome and [[variome]], respectively. Studies in these areas may concern the patterns and trends in [[human DNA]]. The Human Genome Project and The Human Variome Project are examples of large scale studies of the entire human population to collect data which can be analyzed to understand genomic and genetic variation in individuals, respectively.
* The [[Human Genome Project]] is the largest scientific project in the [[history of biology]]. At a cost of $3.8 billion in funding and over a period of 13 years from 1990 to 2003, the project processed through [[DNA sequencing]] the approximately 3 billion base pairs and catalogued the 20,000 to 25,000 genes in human DNA. The project made the data available to all scientific researchers and developed analytical tools for processing this information.<ref>{{cite web|url= http://battelle.org/docs/default-document-library/economic_impact_of_the_human_genome_project.pdf|title= Economic Impact of the Human Genome Project – Battelle|access-date= 1 August 2013|archive-date= 23 December 2012|archive-url= https://web.archive.org/web/20121223040215/http://battelle.org/docs/default-document-library/economic_impact_of_the_human_genome_project.pdf|url-status= dead}}</ref> A particular finding regarding human variability due to difference in DNA made possible by the Human Genome Project is that any two individuals share 99.9% of their [[nucleotide sequences]].<ref>{{cite journal|last1=Chial|first1=Heidi|title=DNA sequencing technologies key to the Human Genome Project|journal=Nature Education|date=2008|volume=1|issue=1|url=http://www.nature.com/scitable/topicpage/dna-sequencing-technologies-key-to-the-human-828|access-date=16 November 2016}}</ref>
* The [[Human Variome Project]] is a similar undertaking with the goal of identification and categorization of the set of  human genetic variation, specifically variations which are medically pertinent. This project will also provide a data repository for further research and analysis of  disease. The Human Variome Project was launched in 2006 and is being run by an international community of researchers and representatives, including collaborators from the [[World Health Organization]] and the [[United Nations Educational, Scientific, and Cultural Organization]].<ref name="pmid17054407">{{cite journal |vauthors=Ring HZ, Kwok PY, Cotton RG |title=Human Variome Project: an international collaboration to catalogue human genetic variation |journal=Pharmacogenomics |volume=7 |issue=7 |pages=969–72 |date=October 2006 |pmid=17054407 |doi=10.2217/14622416.7.7.969 }}</ref>

====Genetic drift====
{{Main|Genetic drift}}
[[Genetic drift]] is one method by which variability occurs in populations.<ref>{{Cite web|url=http://www.nature.com/scitable/definition/random-genetic-drift-genetic-drift-201|title=random genetic drift / genetic drift {{!}} Learn Science at Scitable|website=www.nature.com|access-date=2016-11-16}}</ref> Unlike [[natural selection]], genetic drift occurs when [[allele]]s decrease randomly over time and not as a result of selection bias.<ref>{{Cite web|url=http://evolution.berkeley.edu/evolibrary/article/evo_24|title=Genetic drift|website=evolution.berkeley.edu|access-date=2016-11-16}}</ref> Over a long history, this can cause significant shifts in the underlying genetic distribution of a population. We can model [[genetic drift]] with the Wright-Fisher model. In a population of N with 2N genes, there are two alleles with frequencies p and q. If the previous generation had an allele with frequency p, then the probability that the next generation has k of that allele is:<ref name="Hartl_p112">{{harvnb|Hartl|Clark|2007|p=112}}</ref><ref>{{harvnb|Tian|2008|p=11}}</ref>

<math>{2N \choose k}  p^k q^{2N-k} </math>

Over time, one allele will be fixed when the frequency of that allele reaches 1 and the frequency of the other allele reaches 0. The probability that any allele is fixed is proportional to the frequency of that allele. For two alleles with frequencies p and q, the probability that p will be fixed is p. The expected number of generations for an allele with frequency p to be fixed is:<ref>{{harvnb|Hedrick|2005|p=315}}</ref>

<math>
\bar{T}_\text{fixed} = \frac{-4N_e(1-p) \ln (1-p)}{p}
</math>

Where ''N''<sub>''e''</sub> is the effective population size.<ref name="Charlesworth09">{{cite journal|last=Charlesworth|first=Brian|date=March 2009|title=Fundamental concepts in genetics: Effective population size and patterns of molecular evolution and variation|journal=[[Nature Reviews Genetics]]|volume=10|issue=3|pages=195–205|doi=10.1038/nrg2526|issn=1471-0056|pmid=19204717|s2cid=205484393|author-link=Brian Charlesworth}}</ref>

====Single-nucleotide polymorphism====
{{Main|Single-nucleotide polymorphism}}
[[Single-nucleotide polymorphism]] or SNPs are variations of a single [[nucleotide]]. SNPs can occur in [[Coding region|coding]] or [[Noncoding DNA|non-coding]] regions of genes and on average occur once every 300 [[nucleotide]]s.<ref>{{Cite web|url=https://ghr.nlm.nih.gov/primer/genomicresearch/snp|title=What are single nucleotide polymorphisms (SNPs)?|last=Reference|first=Genetics Home|website=Genetics Home Reference|access-date=2016-11-16}}</ref> SNPs in [[Coding region|coding]] regions can cause [[Synonymous substitution|synonymous]], [[Missense mutation|missense]], and [[nonsense mutation]]s. SNPs have shown to be correlated with drug responses and risk of diseases such as [[Sickle-cell disease|sickle-cell anemia]], [[Alzheimer's disease]], cystic fibrosis, and more.<ref name="ApoE">{{Cite journal|last2=Caselli|first2=R. J.|last3=Reiman|first3=E. M.|last4=Valla|first4=J.|year=2012|title=APOE and neuroenergetics: An emerging paradigm in Alzheimer's disease|journal=Neurobiology of Aging|volume=34|issue=4|pages=1007–17|doi=10.1016/j.neurobiolaging.2012.10.011|pmc=3545040|pmid=23159550|last1=Wolf|first1=A. B.}}</ref>

====DNA fingerprinting====
{{Main| DNA Fingerprinting }}
[[DNA profiling]], whereby a DNA fingerprint is constructed by extracting a DNA sample from body tissue or fluid. Then, it is segmented using restriction enzymes and each segment marked with probes then exposed on X-ray film. The segments form patterns of black bars;the DNA fingerprint.<ref>{{Cite book|url=https://books.google.com/books?id=Yv373szE8B8C&q=A+DNA+fingerprint+is+constructed+by+extracting+a+DNA+sample+from+body+tissue+or+fluid&pg=PA100|title=The Forms of Meaning: Modeling Systems Theory and Semiotic Analysis|last1=Sebeok|first1=Thomas Albert|last2=Danesi|first2=Marcel|date=2000-01-01|publisher=Walter de Gruyter|isbn=9783110167511|language=en}}</ref> DNA Fingerprints are used in conjunction with other methods in order to individuals information in Federal programs such as CODIS (Combined DNA Index System for Missing Persons) in order to help identify individuals <ref>{{Cite web|url=http://www.nij.gov/journals/256/pages/missing-persons.aspx|title=NIJ Journal Issue No. 256, January 2007 {{!}} National Institute of Justice|website=National Institute of Justice|access-date=2016-11-16}}</ref>

==== Mitochondrial DNA ====
[[Mitochondrial DNA]], which is only passed from mother to child. The first human population studies based on mitochondrial DNA were performed by restriction enzyme analyses (RFLPs) and revealed differences between the four ethnic groups (Caucasian, Amerindian, African, and Asian). Differences in mtDNA patterns have also been shown in communities with a different geographic origin within the same ethnic group<ref>{{Cite journal|last1=Yokobori|first1=Shin-ichi|last2=Suzuki|first2=Tsutomu|last3=Watanabe|first3=Kimitsuna|title=Genetic Code Variations in Mitochondria: tRNA as a Major Determinant of Genetic Code Plasticity|journal=Journal of Molecular Evolution|language=en|volume=53|issue=4–5|pages=314–326|doi=10.1007/s002390010221|issn=0022-2844|pmid=11675591|bibcode=2001JMolE..53..314Y|year=2001|s2cid=6475453}}</ref>

====Alloenzymic variation====
[[Alloenzyme|Alloenzymic]] variation, a source of variation that identifies protein variants of the same gene due to amino acid substitutions in proteins. After grinding tissue to release the cytoplasm, wicks are used to absorb the resulting extract and placed in a slit cut into a starch gel. A low current is run across the gel resulting in a positive and negative ends. Proteins are then separated by charge and size, with the smaller and more highly charged molecules moving more quickly across the gel. This techniques does underestimate true genetic variability as there may be an amino acid substitution but if the amino acid is not charged differently than the original no difference in migration will appear it is estimated that approximately 1/3 of the true genetic variation is not expressed by this technique.

====Structural variation====
[[Structural variation]], which can include insertions, deletions, duplications, and mutations in DNA. Within the human population, about 13% of the human genome is defined as structurally variant.

====Phenotypic variation====
{{Details|Phenotype#Phenotypic_variation}}
[[Phenotype#Phenotypic variation|Phenotypic variation]], which accounts for both genetic and epigenetic factors that affect what characteristics are shown. For applications such as organ donations and matching, phenotypic variation of blood type, tissue type, and organ size are considered.