Editing Genetic architecture (section)

== Examples ==
[[File:Evolutionary model of human pigmentation in three continental populations.png|thumb|A speculative framework for the evolutionary history underlying current-day phenotypic variation in human skin pigmentation based on the similarities and differences found in various genotypes.<ref>{{cite journal |last1=Deng |first1=Lian |last2=Xu |first2=Shuhua |title=Adaptation of human skin color in various populations |journal=Hereditas |date=15 June 2017 |volume=155 |issue=1 |pages=1 |doi=10.1186/s41065-017-0036-2 |pmid=28701907 |pmc=5502412 |issn=1601-5223 |doi-access=free }}</ref>]]
A study published in 2006 used phylogeny to compare the genetic architecture of differing human skin color. In this study, researchers were able to suggest a speculative framework for the evolutionary history underlying current-day phenotypic variation in human skin pigmentation based on the similarities and differences they found in the genotype.<ref>{{Cite journal|title = The genetic architecture of normal variation in human pigmentation: an evolutionary perspective and model|journal = Human Molecular Genetics|date = 2006-10-15|issn = 0964-6906|pmid = 16987881|pages = R176–R181|volume = 15|issue = suppl 2|doi = 10.1093/hmg/ddl217|language = en|first1 = Brian|last1 = McEvoy|first2 = Sandra|last2 = Beleza|first3 = Mark D.|last3 = Shriver|doi-access = }}</ref> Evolutionary history is an important consideration in understanding the genetic basis of any trait, and this study was among the first to utilize these concepts in a paired fashion to determine information about the underlying genetics of a phenotypic trait.

In 2013, a group of researchers used [[Genome-wide Association Studies|genome-wide association studies (GWAS)]] and genome-wide interaction studies (GWIS) to determine the risk of [[congenital heart defect]]s in patients with [[Down Syndrome]].<ref>{{Cite journal|last1=Sailani|first1=M. Reza|last2=Makrythanasis|first2=Periklis|last3=Valsesia|first3=Armand|last4=Santoni|first4=Federico A.|last5=Deutsch|first5=Samuel|last6=Popadin|first6=Konstantin|last7=Borel|first7=Christelle|last8=Migliavacca|first8=Eugenia|last9=Sharp|first9=Andrew J.|date=2013-09-01|title=The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome|journal=Genome Research|volume=23|issue=9|pages=1410–1421|doi=10.1101/gr.147991.112|issn=1549-5469|pmc=3759718|pmid=23783273}}</ref> Down Syndrome is a genetic disorder caused by trisomy of human chromosome 21. The current hypothesis regarding congenital heart defect phenotypes in Down Syndrome individuals is that three copies of functional genomic elements on chromosome 21 and genetic variation of chromosome 21 and non-chromosome 21 loci predispose patients to abnormal heart development. This study identified several congenital heart defect risk loci in Down Syndrome individuals, as well as three [[Copy-number variation|copy number variation (CNV)]] regions that may contribute to congenital heart defects in Down Syndrome individuals.

Another study, which was published in 2014, sought to identify the genetic architecture of psychiatric disorders. The researchers in this study suggested that there are a large number of contributing loci that are related to various psychiatric disorders.<ref>{{Cite journal|last1=Gratten|first1=Jacob|last2=Wray|first2=Naomi R. |authorlink2=Naomi Wray |last3=Keller|first3=Matthew C.|last4=Visscher|first4=Peter M.|date=2014-06-01|title=Large-scale genomics unveils the genetic architecture of psychiatric disorders|journal=Nature Neuroscience|volume=17|issue=6|pages=782–790|doi=10.1038/nn.3708|issn=1546-1726|pmc=4112149|pmid=24866044}}</ref> Additionally, they, like many others, suggested that the genetic risk of psychiatric disorders involves the combined effects of many common variants with small effects - in other words, the small effects of a wide number of variants at specific loci add together to produce a large, combined effect on the overall phenotype of the individual. They also acknowledged the presence of large but rare mutations that have a large effect on phenotype. This study showcases the intricacy of genetic architecture by providing an example of many different SNPs and mutations working together, each with a varying effect, to generate a given phenotype.

Other studies regarding genetic architecture are many and varied, but most use similar types of analyses to provide specific information regarding loci involved in producing a phenotype. A study of the human immune system in 2015<ref>{{Cite journal|last1=Roederer|first1=Mario|last2=Quaye|first2=Lydia|last3=Mangino|first3=Massimo|last4=Beddall|first4=Margaret H.|last5=Mahnke|first5=Yolanda|last6=Chattopadhyay|first6=Pratip|last7=Tosi|first7=Isabella|last8=Napolitano|first8=Luca|last9=Terranova Barberio|first9=Manuela|date=2015-04-09|title=The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis|journal=Cell|language=English|volume=161|issue=2|pages=387–403|doi=10.1016/j.cell.2015.02.046|issn=0092-8674|pmc=4393780|pmid=25772697}}</ref> uses the same general concepts to identify several loci involved in the development of the immune system, but, like the other studies outlined here, failed to consider other aspects of genetic architecture, such as environmental influences. Unfortunately, many other aspects of genetic architecture remain difficult to quantify.

Although there are a few studies that seek to explore the other aspects of genetic architecture, there is little ability with current technologies to link all of the pieces together to build a truly comprehensive model of genetic architecture. For example, in 2003, a study of genetic architecture and the environment was able to show an association of social environment with variation in body size in ''[[Drosophila melanogaster]]''.<ref>{{Cite journal|last=Wolf|first=Jason B.|date=2003-04-15|title=Genetic architecture and evolutionary constraint when the environment contains genes|journal=Proceedings of the National Academy of Sciences|volume=100|issue=8|pages=4655–4660|doi=10.1073/pnas.0635741100|issn=0027-8424|pmc=153611|pmid=12640144|doi-access=free}}</ref> However, this study was not able to tie a direct link to specific genes involved in this variation.