Editing Iron overload (section)

== Identification of genetic factors ==
Although it was known most of the 20th century that most cases of hemochromatosis were inherited, they were incorrectly assumed to depend on a single gene.<ref name="isbn1-58829-202-9">{{cite book |author1=Cam Patterson |author2=Marschall S. Runge |title=Principles of molecular medicine |publisher=Humana Press |location=Totowa, NJ |year=2006 |pages=567  |isbn=978-1-58829-202-5 }}</ref>

In 1935 J.H. Sheldon, a British physician, described the link to iron metabolism for the first time as well as demonstrating its hereditary nature.<ref name=":0" />

In 1996 Feder and colleagues identified the hemochromatosis gene, ''HFE'' gene. Felder found that the ''HFE'' gene has two main mutations, causing amino acid substitutions C282Y and H63D, which were the main cause of hereditary hemochromatosis.<ref name=":0"/><ref>{{Cite journal|last1=Feder|first1=J.N.|last2=Gnirke|first2=A.|last3=Thomas|first3=W.|last4=Tsuchihashi|first4=Z.|last5=Ruddy|first5=D.A.|last6=Basava|first6=A.|last7=Dormishian|first7=F.|last8=Domingo|first8=R.|last9=Ellis|first9=M.C.|date=August 1996|title=A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis|journal=Nature Genetics|language=en|volume=13|issue=4|pages=399–408|doi=10.1038/ng0896-399|pmid=8696333|s2cid=26239768}}</ref> The next year the CDC and the National Human Genome Research Institute sponsored an examination of hemochromatosis following the discovery of the ''HFE'' gene, which helped lead to the population screenings and estimates that are still being used today.<ref>{{Cite journal|last1=Burke|first1=Wylie|last2=Thomson|first2=Elizabeth|last3=Khoury|first3=Muin J.|last4=McDonnell|first4=Sharon M.|last5=Press|first5=Nancy|last6=Adams|first6=Paul C.|last7=Barton|first7=James C.|last8=Beutler|first8=Ernest|last9=Brittenham|first9=Gary|date=1998-07-08|title=Hereditary Hemochromatosis: Gene Discovery and Its Implications for Population-Based Screening|journal=JAMA|language=en|volume=280|issue=2|pages=172–78|doi=10.1001/jama.280.2.172|pmid=9669792|issn=0098-7484}}</ref>