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{{Short description|American geneticist (1937–2022)}}
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{{Use mdy dates|date=March 2024}}
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{{short description|American geneticist}}

{{Infobox scientist
{{Infobox scientist
|name = Haig H. Kazazian, Jr.
|name = Haig Kazazian
|image =
|image =
|caption =
|caption =
|birth_date = {{birth date|1937|07|30}}<ref name="LOC">{{cite web |title=Kazazian, Haig H., Jr., 1937- |url=https://lccn.loc.gov/n89111227 |website=Library of Congress Authorities |access-date=7 February 2022}}</ref>
|birth_date = {{birth date|1937|07|30}}<ref name="LOC">{{cite web |title=Kazazian, Haig H., Jr., 1937- |url=https://lccn.loc.gov/n89111227 |website=Library of Congress Authorities |access-date=7 February 2022}}</ref>
|birth_nane = Haig Hagop Kazazian, Jr.
|birth_name = Haig Hagop Kazazian Jr.
|birth_place = [[Toledo, Ohio]]
|birth_place = [[Toledo, Ohio]]
|death_date = {{death date and age|2022|01|20|1937|07|30}}
|death_date = {{death date and age|2022|01|20|1937|07|30}}
|death_place = [[Towson, Maryland]].
|death_place = [[Towson, Maryland]]
|workplaces = [[Johns Hopkins University School of Medicine]], [[University of Pennsylvania]]
|workplaces = [[Johns Hopkins University School of Medicine]], [[University of Pennsylvania]]
|field = [[Genetics]]
|field = [[Genetics]]
|alma_mater = [[Dartmouth College]], [[Johns Hopkins University School of Medicine]]
|alma_mater = [[Dartmouth College]], [[Johns Hopkins University School of Medicine]]
}}
}}


'''Haig H. Kazazian, Jr.''' (July 30, 1937-January 19/20, 2022) was a professor in the Department of Genetic Medicine at [[Johns Hopkins University School of Medicine]], [[Baltimore, Maryland]]. <ref name="Wasta">{{cite news |last1=Wasta |first1=Vanessa |last2=Butch |first2=Rachel |title=Haig Kazazian, pioneer in genetic medicine, dies at 84 |url=https://hub.jhu.edu/2022/02/02/haig-kazazian-obituary/ |access-date=6 February 2022 |work=The Hub |date=2 February 2022 |language=en}}</ref> Kazazian was an elected member of the [[National Academy of Sciences]]<ref name="NAS"/> and the [[American Academy of Arts and Sciences]].<ref name="AAAS"/>
'''Haig Hagop Kazazian Jr.''' (July 30, 1937 – January 19/20, 2022) was an American professor in the Department of Genetic Medicine at [[Johns Hopkins University School of Medicine]] in [[Baltimore, Maryland]].<ref name="Wasta">{{cite news |last1=Wasta |first1=Vanessa |last2=Butch |first2=Rachel |title=Haig Kazazian, pioneer in genetic medicine, dies at 84 |url=https://hub.jhu.edu/2022/02/02/haig-kazazian-obituary/ |access-date=6 February 2022 |work=The Hub |date=2 February 2022 |language=en}}</ref> Kazazian was an elected member of the [[National Academy of Sciences]]<ref name="NAS"/> and the [[American Academy of Arts and Sciences]].<ref name="AAAS"/>


Kazazian determined the molecular basis of single-gene [[genetic disorders]] such as [[hemoglobinopathies]] and [[hemophilia]] and introduced prenatal diagnosis for such disorders. His group was the first to identify a disease-causing mutation resulting from [[jumping genes]] in humans.<ref name="Singer"/> After this discovery, he focused on basic research into LINE [[retrotransposition]] in humans and its implications for disease.<ref name="Jump"/>
Kazazian determined the molecular basis of single-gene [[genetic disorders]] such as [[hemoglobinopathies]] and [[hemophilia]] and introduced prenatal diagnosis for such disorders. His group was the first to identify a disease-causing mutation resulting from [[jumping genes]] in humans.<ref name="Singer"/> After this discovery, he focused on basic research into LINE [[retrotransposition]] in humans and its implications for disease.<ref name="Jump"/>


==Early life and education==
==Early life and education==
Kazazian's Armenian father (also Haig H. Kazazian) was from [[Kayseri, Turkey|Kayseri, Turkey]]. He was sent to the [[Ras al-Ayn Camps|Ras el Ain concentration camp]] in [[Syria]] as part of the [[Armenian genocide]], but escaped in 1918 and arrived in the U.S. in 1923. <ref name="Kazazian"/><ref name="Antonarakis"/><ref name="Azar"/> Kazazian's mother Hermine<ref>{{cite news |title=Hermine A. Kazazian Obituary |date=2007 |work=The Detroit News |url=https://www.legacy.com/us/obituaries/detroitnews/name/hermine-kazazian-obituary?pid=182748669 |access-date=7 February 2022}}</ref> left [[Istanbul]] and arrived in the U.S. in 1920.<ref name="Kazazian"/><ref name="Antonarakis"/><ref name="Azar"/> They married on January 1, 1929.<ref name="Kazazian"/>
Haig Hagop Kazazian Jr.'s Armenian father was from [[Kayseri]], Turkey. He was sent to the [[Ras al-Ayn Camps|Ras el Ain concentration camp]] in Syria as part of the [[Armenian genocide]], but escaped in 1918 and arrived in the U.S. in 1923.<ref name="Kazazian"/><ref name="Antonarakis"/><ref name="Azar"/> Kazazian's mother, Hermine,<ref>{{cite news |title=Hermine A. Kazazian Obituary |date=2007 |work=The Detroit News |url=https://www.legacy.com/us/obituaries/detroitnews/name/hermine-kazazian-obituary?pid=182748669 |access-date=7 February 2022}}</ref> left [[Istanbul]] and arrived in the U.S. in 1920.<ref name="Kazazian"/><ref name="Antonarakis"/><ref name="Azar"/> They married on January 1, 1929.<ref name="Kazazian"/>


Haig Hagop Kazazian, Jr. was born in [[Toledo, Ohio]]<ref name="Antonarakis"/> on July 30, 1937.<ref name="LOC"/> He grew up speaking Armenian, Turkish and English.<ref name="Antonarakis"/>
Haig Jr. was born in [[Toledo, Ohio]],<ref name="Antonarakis"/> on July 30, 1937.<ref name="LOC"/> He grew up speaking Armenian, Turkish and English.<ref name="Antonarakis"/> He attended [[Dartmouth College]], receiving his A.B. degree from Dartmouth College in 1959, followed by a two-year program at [[Dartmouth Medical School]]. He completed his M.D. degree at [[Johns Hopkins University School of Medicine]]<ref name="InformIT"/> in 1962, and interned in pediatrics at the [[University of Minnesota]].<ref name="Antonarakis"/>

Kazazian attended [[Dartmouth College]], receiving his A.B. degree from Dartmouth College in 1959, followed by a two-year program at [[Dartmouth Medical School]]. He completed his M.D. degree at [[Johns Hopkins University School of Medicine]]<ref name="InformIT"/> in 1962<ref name="Antonarakis"/> and interned in pediatrics at the [[University of Minnesota]].<ref name="Antonarakis"/>


==Career==
==Career==
Kazazian returned to Baltimore, Maryland as a postdoctoral fellow, studying the genetics of [[fruit flies]] and X chromosome inactivation with [[Barton Childs]] at Johns Hopkins (1964–1966)<ref name="Rader"/><ref name="Antonarakis"/><ref name="Azar"/> In 1966 he joined [[Harvey Itano]] at the [[National Institutes of Health]],<ref name="InformIT">{{cite web |title=Haig H. Kazazian |url=https://www.informit.com/authors/bio/13d0e792-2184-4c09-ad1a-2bb4d84be698 |website=InformIT |access-date=5 February 2022}}</ref> working as a staff associate for the [[US Public Health Service]].<ref name="Kazazian">{{cite journal |last1=Kazazian |first1=Haig H. |title=A Long, Fulfilling Career in Human Genetics |journal=Annual Review of Genomics and Human Genetics |date=31 August 2021 |volume=22 |issue=1 |pages=27–53 |doi=10.1146/annurev-genom-111620-095614 |url=https://doi.org/10.1146/annurev-genom-111620-095614 |access-date=5 February 2022 |issn=1527-8204}}</ref> In Itano's labotory, Kazazian worked on [[hemoglobin]] regulation.<ref name="Azar"/>
Kazazian returned to Baltimore, Maryland as a postdoctoral fellow, studying the genetics of [[Drosophilidae|fruit flies]] and X chromosome inactivation with [[Barton Childs]] at Johns Hopkins (1964–1966)<ref name="Rader"/><ref name="Antonarakis"/><ref name="Azar"/> In 1966, he joined [[Harvey Itano]] at the [[National Institutes of Health]],<ref name="InformIT">{{cite web |title=Haig H. Kazazian |url=https://www.informit.com/authors/bio/13d0e792-2184-4c09-ad1a-2bb4d84be698 |website=InformIT |access-date=5 February 2022}}</ref> working as a staff associate for the [[US Public Health Service]].<ref name="Kazazian">{{cite journal |last1=Kazazian |first1=Haig H. |title=A Long, Fulfilling Career in Human Genetics |journal=Annual Review of Genomics and Human Genetics |date=31 August 2021 |volume=22 |issue=1 |pages=27–53 |doi=10.1146/annurev-genom-111620-095614 |pmid=33945751 |s2cid=233744364 |issn=1527-8204|doi-access=free }}</ref> In Itano's labotory, Kazazian worked on [[hemoglobin]] regulation.<ref name="Azar"/>


Kazazian joined the faculty at Johns Hopkins in 1969.<ref name="Wasta"/> He became a full professor, heading the Pediatric Genetics Unit, in 1977.<ref name="InformIT"/> In 1979,<ref name="Kazazian"/> he established one of the first DNA diagnostic laboratories, providing molecular detection facilities for identifying monogenic disorders. He introduced prenatal diagnosis for hemoglobin disorders.<ref name="Wasta"/> In 1988, Kazazian became Director of the Center for Medical Genetics at Johns Hopkins.<ref name="InformIT"/> From 1988 to 1994, he and [[Maxine Singer]] at the National Institutes of Health (NIH) held joint quarterly lab meetings, sharing their knowledge of the biochemistry and genetics.<ref name="Mobile">{{cite book |last1=Kazazian |first1=Haig H. |title=Mobile DNA: Finding Treasure in Junk |date=18 March 2011 |publisher=FT Press |location=Upper Saddle River, NJ |isbn=978-0-13-257525-6 |url=https://books.google.com/books?id=UGCPUtBHQXcC&pg=PT66 |access-date=7 February 2022 |language=en}}</ref>
Kazazian joined the faculty at Johns Hopkins in 1969.<ref name="Wasta"/> He became a full professor, heading the Pediatric Genetics Unit, in 1977.<ref name="InformIT"/> In 1979,<ref name="Kazazian"/> he established one of the first DNA diagnostic laboratories, providing molecular detection facilities for identifying monogenic disorders. He introduced prenatal diagnosis for hemoglobin disorders.<ref name="Wasta"/> In 1988, Kazazian became Director of the Center for Medical Genetics at Johns Hopkins.<ref name="InformIT"/> From 1988 to 1994, he and [[Maxine Singer]] at the National Institutes of Health (NIH) held joint quarterly lab meetings, sharing their knowledge of the biochemistry and genetics.<ref name="Mobile">{{cite book |last1=Kazazian |first1=Haig H. |title=Mobile DNA: Finding Treasure in Junk |date=March 18, 2011 |publisher=FT Press |location=Upper Saddle River, NJ |isbn=978-0-13-257525-6 |url=https://books.google.com/books?id=UGCPUtBHQXcC&pg=PT66 |access-date=February 7, 2022 |language=en}}</ref>


Kazazian and [[Richard Cotton (geneticist)|Richard Cotton]] were founding co-editors of the journal ''[[Human Mutation]]'', which appeared in 1992.<ref>{{cite journal|title=Infectious Enthusiasm! Larger than Life! That Laugh! That Smile! In Loving Memory of Richard G.H. (Dick) Cotton | doi=10.1002/humu.22990 | pmid=27030029 | volume=37|issue = 6|journal=Human Mutation|pages=598–615|year = 2016| s2cid=205923182 }}</ref>
Kazazian and [[Richard Cotton (geneticist)|Richard Cotton]] were founding co-editors of the journal ''[[Human Mutation]]'', which appeared in 1992.<ref>{{cite journal|title=Infectious Enthusiasm! Larger than Life! That Laugh! That Smile! In Loving Memory of Richard G.H. (Dick) Cotton | doi=10.1002/humu.22990 | pmid=27030029 | volume=37|issue = 6|journal=Human Mutation|pages=598–615|year = 2016| s2cid=205923182 |doi-access=free}}</ref>
Kazazian became a co-editor of the journal ''[[Mobile DNA (journal)|Mobile DNA]]'' in 2015.<ref name="Rose">{{cite journal |last1=Rose |first1=Sam |title=Mobile DNA welcomes new Editors-in-Chief, Marlene Belfort and Haig Kazazian |journal=On Biology |date=17 April 2015 |url=https://blogs.biomedcentral.com/on-biology/2015/04/17/mobile-dna-welcomes-new-editors-chief-marlene-belfort-haig-kazazian/ |access-date=7 February 2022}}</ref>
Kazazian became a co-editor of the journal ''[[Mobile DNA (journal)|Mobile DNA]]'' in 2015.<ref name="Rose">{{cite journal |last1=Rose |first1=Sam |title=Mobile DNA welcomes new Editors-in-Chief, Marlene Belfort and Haig Kazazian |journal=On Biology |date=17 April 2015 |url=https://blogs.biomedcentral.com/on-biology/2015/04/17/mobile-dna-welcomes-new-editors-chief-marlene-belfort-haig-kazazian/ |access-date=7 February 2022}}</ref>


In 1994 Kazazian became Chair of the Department of Genetics at the [[University of Pennsylvania School of Medicine]], holding the position until 2006.<ref name="Rader"/> He remained at the University of Pennsylvaniaf as the Seymour Gray Professor of Molecular Medicine in Genetics from 2006-2010.<ref name="InformIT"/>
In 1994, he became Chair of the Department of Genetics at the [[University of Pennsylvania School of Medicine]], holding the position until 2006.<ref name="Rader"/> He remained at the University of Pennsylvaniaf as the Seymour Gray Professor of Molecular Medicine in Genetics from 2006 to 2010.<ref name="InformIT"/>


In 1999, Kazazian and Arupa Ganguly joined the plaintiffs for ''[[Association for Molecular Pathology v. Myriad Genetics, Inc.]]'',<ref name="Wasta"/><ref name="Butanis">{{cite news |last1=Butanis |first1=Benjamin |title=Supreme Court Rules on Gene Patent Case |url=https://www.hopkinsmedicine.org/news/stories/supreme_court_rules_on_gene_patent_case.html |access-date=6 February 2022 |work=Johns Hopkins Medicine |language=en}}</ref> after they were served with a cease-and-desist letter demanding that they stop [[breast cancer]] screenings for the [[BRCA1]] and [[BRCA2]] genes.<ref name="Kazazian"/>
In 1999, Kazazian and Arupa Ganguly joined the plaintiffs for ''[[Association for Molecular Pathology v. Myriad Genetics, Inc.]]'',<ref name="Wasta"/><ref name="Butanis">{{cite news |last1=Butanis |first1=Benjamin |title=Supreme Court Rules on Gene Patent Case |url=https://www.hopkinsmedicine.org/news/stories/supreme_court_rules_on_gene_patent_case.html |access-date=6 February 2022 |work=Johns Hopkins Medicine |language=en}}</ref> after they were served with a cease-and-desist letter demanding that they stop [[breast cancer]] screenings for the [[BRCA1]] and [[BRCA2]] genes.<ref name="Kazazian"/>
In a unanimous ruling in 2013, the Supreme Court ruled that companies cannot patent parts of naturally occurring human genes. The Court stated that "a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but manmade cDNA is patent eligible because it is not naturally occurring."<ref name="Goldstein">{{cite news |last1=Goldstein |first1=Tom |title=Details on Association for Molecular Pathology v. Myriad Genetics, Inc. |url=https://www.scotusblog.com/2013/06/details-on-association-for-molecular-pathology-v-myriad-genetics-inc/ |access-date=6 February 2022 |work=SCOTUSblog |date=13 June 2013}}</ref><ref name="Brandom">{{cite news |last1=Brandom |first1=Russell |title=After Supreme Court ruling, don't count out gene patenting quite yet |url=https://www.theverge.com/2013/6/14/4430748/supreme-court-ruling-on-gene-patents-is-a-compromise |access-date=6 February 2022 |work=The Verge |date=14 June 2013 |language=en}}</ref><ref name="Marbella">{{cite news |last1=Marbella |first1=Jean |title=Ban on patenting DNA cheers researchers |url=https://www.baltimoresun.com/health/bs-md-scotus-gene-patent-react-20130613-story.html |access-date=6 February 2022 |work=The Baltimore Sun |date=June 13, 2013}}</ref>
In a unanimous ruling in 2013, the Supreme Court ruled that companies cannot patent parts of naturally occurring human genes. The Court stated that "a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but manmade cDNA is patent eligible because it is not naturally occurring."<ref name="Goldstein">{{cite news |last1=Goldstein |first1=Tom |title=Details on Association for Molecular Pathology v. Myriad Genetics, Inc. |url=https://www.scotusblog.com/2013/06/details-on-association-for-molecular-pathology-v-myriad-genetics-inc/ |access-date=6 February 2022 |work=SCOTUSblog |date=13 June 2013}}</ref><ref name="Brandom">{{cite news |last1=Brandom |first1=Russell |title=After Supreme Court ruling, don't count out gene patenting quite yet |url=https://www.theverge.com/2013/6/14/4430748/supreme-court-ruling-on-gene-patents-is-a-compromise |access-date=6 February 2022 |work=The Verge |date=14 June 2013 |language=en}}</ref><ref name="Marbella">{{cite news |last1=Marbella |first1=Jean |title=Ban on patenting DNA cheers researchers |url=https://www.baltimoresun.com/health/bs-md-scotus-gene-patent-react-20130613-story.html |access-date=6 February 2022 |work=The Baltimore Sun |date=June 13, 2013}}</ref> In July 2010, Kazazian returned to Johns Hopkins, holding the position of a Professor in the Institute of Genetic Medicine.<ref name="InformIT"/> He closed his laboratory there in 2020.<ref name="NAS"/>


⚫
His book ''Mobile DNA: Finding Treasure in Junk'' (2011) gives an overview of research on transposable elements. It does a "remarkable job" of discussing early contributors, the development of computational biology, and the field of mobile DNA and retrotransposable elements.<ref name="Batzer">{{cite journal |last1=Batzer |first1=Mark A. |title=Mobile DNA: Finding Treasure in Junk |journal=American Journal of Human Genetics |date=11 July 2013 |volume=93 |issue=1 |pages=5 |doi=10.1016/j.ajhg.2013.06.001 |pmc=3710766 |issn=0002-9297}}</ref> Although the initial chapters of background information on the field have been criticized as less interesting than later and more personal chapters, the account is credited with vividly illustrating "both the destructive and constructive facets of transposition in the genome".<ref name="Feschotte">{{cite journal |last1=Feschotte |first1=Cédric |title=Review of Mobile DNA - finding treasure in junk by Haig H Kazazian |journal=Mobile DNA |date=3 October 2012 |volume=3 |issue=1 |pages=16 |doi=10.1186/1759-8753-3-16 |s2cid=1024114 |issn=1759-8753|doi-access=free |pmc=3517452 }}</ref>
In July 2010, Kazazian returned to Johns Hopkins, holding the position of a Professor in the Institute of Genetic Medicine.<ref name="InformIT"/> He closed his laboratory there in 2020.<ref name="NAS"/>

⚫
Kazazian's book ''Mobile DNA: Finding Treasure in Junk'' (2011) gives an overview of research on transposable elements. It does a "remarkable job" of discussing early contributors, the development of computational biology, and the field of mobile DNA and retrotransposable elements.<ref name="Batzer">{{cite journal |last1=Batzer |first1=Mark A. |title=Mobile DNA: Finding Treasure in Junk |journal=American Journal of Human Genetics |date=11 July 2013 |volume=93 |issue=1 |pages=5 |doi=10.1016/j.ajhg.2013.06.001 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3710766/ |access-date=6 February 2022 |issn=0002-9297}}</ref> Although the initial chapters of background information on the field have been criticized as less interesting than later and more personal chapters, the account is credited with vividly illustrating "both the destructive and constructive facets of transposition in the genome".<ref name="Feschotte">{{cite journal |last1=Feschotte |first1=Cédric |title=Review of Mobile DNA - finding treasure in junk by Haig H Kazazian |journal=Mobile DNA |date=3 October 2012 |volume=3 |issue=1 |pages=16 |doi=10.1186/1759-8753-3-16 |url=https://mobilednajournal.biomedcentral.com/articles/10.1186/1759-8753-3-16 |access-date=7 February 2022 |issn=1759-8753}}</ref>


Kazazian died on January 19<ref name="Wasta"/> or 20, 2022 in [[Towson, Maryland]].<ref name="Rader">{{cite news |last1=Rader |first1=Daniel J. |title=Announcement from Dr. Rader: Death of Haig H Kazazian, Jr, MD |url=https://genetics.med.upenn.edu/announcement-from-dr-rader-death-of-haig-h-kazazian-jr-md/ |access-date=7 February 2022 |work=Penn Genetics |date=25 January 2022}}</ref>
Kazazian died on January 19<ref name="Wasta"/> or 20, 2022 in [[Towson, Maryland]].<ref name="Rader">{{cite news |last1=Rader |first1=Daniel J. |title=Announcement from Dr. Rader: Death of Haig H Kazazian, Jr, MD |url=https://genetics.med.upenn.edu/announcement-from-dr-rader-death-of-haig-h-kazazian-jr-md/ |access-date=7 February 2022 |work=Penn Genetics |date=25 January 2022}}</ref>
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Much of his early research focused on the regulation of hemoglobin synthesis and its implications for the human blood disorder [[β-thalassemia]].<ref name="Azar"/>
Much of his early research focused on the regulation of hemoglobin synthesis and its implications for the human blood disorder [[β-thalassemia]].<ref name="Azar"/>
Using information on [[β-globin]] DNA [[polymorphisms]] from [[Stylianos Antonarakis]] and others, Kazazian helped develop methods for prenatal diagnosis of [[sickle cell anemia]]. Coining the term [[haplotypes]] for certain types of polymorphisms, Kazazian collaborated with [[Stuart Orkin]] to characterize the mutations causing [[beta-thalassemia]].<ref name="Azar"/><ref name="Wasta"/> He used haplotypes to classify β-thalassemia mutations in patients from around the world and to prenatally identify β-thalassemia.<ref name="Rader"/>
Using information on [[β-globin]] DNA [[Genetic polymorphism|polymorphism]]s from [[Stylianos Antonarakis]] and others, Kazazian helped develop methods for prenatal diagnosis of [[sickle cell anemia]]. Coining the term [[haplotypes]] for certain types of polymorphisms, Kazazian collaborated with [[Stuart Orkin]] to characterize the mutations causing [[beta-thalassemia]].<ref name="Azar"/><ref name="Wasta"/> He used haplotypes to classify β-thalassemia mutations in patients from around the world and to prenatally identify β-thalassemia.<ref name="Rader"/>


In the 1980s, Kazazian began to study the [[factor 8]] blood-clotting gene, which was known to be defective in [[hemophilia A]]. Lab member Hagop Youssoufian found a [[long interspersed nuclear element]] (LINE) insertion, a [[mobile DNA]] element or transposon colloquially known as a “jumping gene”. Jumping genes were discovered in [[maize]] by [[Barbara McClintock]].<ref name="Azar"/> The Kazazian lab was the first to discover a jumping gene in humans, and to demonstrate that a transposable element caused disease in man via [[insertional mutagenesis]].<ref name="AAAS"/><ref name="Singer">{{cite journal |last1=Singer |first1=Maxine F. |title=From Genomic Junk to Human Disease |journal=Proceedings of the American Philosophical Society |date=1994 |volume=138 |issue=1 |pages=11–24 |url=https://www.jstor.org/stable/986702 |access-date=7 February 2022 |issn=0003-049X}}</ref><ref name="Wasta"/> Kazazian expanded this work to mouse models, providing evidence that active retrotransposons occur in other mammals.<ref name="AAAS"/>
In the 1980s, Kazazian began to study the [[factor 8]] blood-clotting gene, which was known to be defective in [[hemophilia A]]. Lab member Hagop Youssoufian found a [[long interspersed nuclear element]] (LINE) insertion, a [[mobile DNA]] element or transposon colloquially known as a “jumping gene”. Jumping genes were discovered in [[maize]] by [[Barbara McClintock]].<ref name="Azar"/> The Kazazian lab was the first to discover a jumping gene in humans, and to demonstrate that a transposable element caused disease in man via [[insertional mutagenesis]].<ref name="AAAS"/><ref name="Singer">{{cite journal |last1=Singer |first1=Maxine F. |title=From Genomic Junk to Human Disease |journal=Proceedings of the American Philosophical Society |date=1994 |volume=138 |issue=1 |pages=11–24 |jstor=986702 |url=https://www.jstor.org/stable/986702 |access-date=7 February 2022 |issn=0003-049X}}</ref><ref name="Wasta"/> Kazazian expanded this work to mouse models, providing evidence that active retrotransposons occur in other mammals.<ref name="AAAS"/>


Since then Kazazian has focused on basic research into LINE [[retrotransposition]] in humans, and the role of jumping genes in human disease. Retrotransposons copy and insert themselves into new locations in the genome.<ref name="Jump"/>
Since then Kazazian has focused on basic research into LINE [[retrotransposition]] in humans, and the role of jumping genes in human disease. Retrotransposons copy and insert themselves into new locations in the genome.<ref name="Jump"/>
As a postdoctoral fellow with Kazazian, [[John Moran (geneticist)|John Moran]] developed a cell culture assay to detect retrotransposition. They determined that the average human genome has 80–100 active LINE-1 (L1) retrotransposons, a handful of which are very active.<ref name="Azar"/><ref name="Jump"/><ref name="Ishak">{{cite journal |last1=Ishak |first1=Charles A. |last2=De Carvalho |first2=Daniel D. |title=Reactivation of Endogenous Retroelements in Cancer Development and Therapy |journal=Annual Review of Cancer Biology |date=9 March 2020 |volume=4 |issue=1 |pages=159–176 |doi=10.1146/annurev-cancerbio-030419-033525 |url=https://doi.org/10.1146/annurev-cancerbio-030419-033525 |access-date=7 February 2022 |issn=2472-3428}}</ref> Kazazian's lab also discovered SVA, a [[short interspersed nuclear element]] (SINE) and active jumping gene.<ref name="Azar"/>
As a postdoctoral fellow with Kazazian, [[John Moran (geneticist)|John Moran]] developed a cell culture assay to detect retrotransposition. They determined that the average human genome has 80–100 active LINE-1 (L1) retrotransposons, a handful of which are very active.<ref name="Azar"/><ref name="Jump"/><ref name="Ishak">{{cite journal |last1=Ishak |first1=Charles A. |last2=De Carvalho |first2=Daniel D. |title=Reactivation of Endogenous Retroelements in Cancer Development and Therapy |journal=Annual Review of Cancer Biology |date=9 March 2020 |volume=4 |issue=1 |pages=159–176 |doi=10.1146/annurev-cancerbio-030419-033525 |s2cid=213919601 |issn=2472-3428|doi-access=free }}</ref>
In addition to understanding diseases, studying L1 insertions enables researchers to learn about human diversity.<ref name="Jump">{{cite news |title=Johns Hopkins Researchers Capture Jumping Genes |url=https://www.hopkinsmedicine.org/news/media/releases/johns_hopkins_researchers_capture_jumping_genes |access-date=6 February 2022 |work=Johns Hopkins Medicine |date=February 4, 2011 |language=en}}</ref>
In addition to understanding diseases, studying L1 insertions enables researchers to learn about human diversity.<ref name="Jump">{{cite news |title=Johns Hopkins Researchers Capture Jumping Genes |url=https://www.hopkinsmedicine.org/news/media/releases/johns_hopkins_researchers_capture_jumping_genes |access-date=6 February 2022 |work=Johns Hopkins Medicine |date=February 4, 2011 |language=en}}</ref>


Kazazian's studies with rodents suggest that retrotransposition tends to occur during early embryonic development.<ref name="Azar"/> Kazazian found that retrotransposon mobility causes shuffling of [[exons]] and their flanking sequences, a discovery with important implications for the understanding of [[evolution]].<ref name="AAAS"/>
Kazazian's studies with rodents suggest that retrotransposition tends to occur during early embryonic development.<ref name="Azar"/> Kazazian found that retrotransposon mobility causes shuffling of [[exons]] and their flanking sequences, a discovery with important implications for the understanding of [[evolution]].<ref name="AAAS"/>


Kazazian has also investigated the possibility that LINE-1 jumping genes play a role in [[cancer]]. He and others have observed instances of new insertions of jumping genes in some cancers, but he could not determine whether LINE-1 genes drive cancer development or are a side effect of cancer.<ref name="Ives">{{cite news |last1=Ives |first1=James |title=Jumping genes: a marker for early cancer diagnosis? An interview with Dr Kazazian |url=https://www.news-medical.net/news/20151006/Jumping-genes-a-marker-for-early-cancer-diagnosis-An-interview-with-Dr-Kazazian.aspx |access-date=7 February 2022 |work=News-Medical.net |date=6 October 2015 |language=en}}</ref>
Kazazian investigated the possibility that LINE-1 jumping genes play a role in [[cancer]]. He and others have observed instances of new insertions of jumping genes in some cancers, but he could not determine whether LINE-1 genes drive cancer development or are a side effect of cancer.<ref name="Ives">{{cite news |last1=Ives |first1=James |title=Jumping genes: a marker for early cancer diagnosis? An interview with Dr Kazazian |url=https://www.news-medical.net/news/20151006/Jumping-genes-a-marker-for-early-cancer-diagnosis-An-interview-with-Dr-Kazazian.aspx |access-date=7 February 2022 |work=News-Medical.net |date=6 October 2015 |language=en}}</ref>


==Awards==
==Awards==
* 2018, Member, Institute of Medicine of the [[National Academy of Sciences]]<ref name="Azar">{{cite journal |last1=Azar |first1=Beth |title=Profile of Haig H. Kazazian Jr. |journal=Proceedings of the National Academy of Sciences |date=22 December 2020 |volume=117 |issue=51 |pages=32185–32188 |doi=10.1073/pnas.2023398117 |url=https://www.pnas.org/content/117/51/32185 |access-date=6 February 2022 |language=en |issn=0027-8424}}</ref><ref name="NAS">{{cite web |title=Haig H. Kazazian |url=http://www.nasonline.org/member-directory/members/2617.html |website=National Academy of Sciences |access-date=7 February 2022}}</ref>
* 2018, Member, [[National Academy of Sciences]]<ref name="Azar">{{cite journal |last1=Azar |first1=Beth |title=Profile of Haig H. Kazazian Jr. |journal=Proceedings of the National Academy of Sciences |date=22 December 2020 |volume=117 |issue=51 |pages=32185–32188 |doi=10.1073/pnas.2023398117 |pmid=33273116 |pmc=7768710 |bibcode=2020PNAS..11732185A |language=en |issn=0027-8424|doi-access=free }}</ref><ref name="NAS">{{cite web |title=Haig H. Kazazian |url=http://www.nasonline.org/member-directory/members/2617.html |website=National Academy of Sciences |access-date=7 February 2022}}</ref>
* 2008, [[William Allan Award]], [[American Society of Human Genetics]]<ref name="Antonarakis">{{cite journal |last1=Antonarakis |first1=Stylianos E. |title=William Allan Award Introduction: Haig H. Kazazian, Jr. |journal=American Journal of Human Genetics |date=13 February 2009 |volume=84 |issue=2 |pages=103–104 |doi=10.1016/j.ajhg.2009.01.002 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667997/ |access-date=6 February 2022 |issn=0002-9297}}</ref>
* 2008, [[William Allan Award]], [[American Society of Human Genetics]]<ref name="Antonarakis">{{cite journal |last1=Antonarakis |first1=Stylianos E. |title=William Allan Award Introduction: Haig H. Kazazian, Jr. |journal=American Journal of Human Genetics |date=13 February 2009 |volume=84 |issue=2 |pages=103–104 |doi=10.1016/j.ajhg.2009.01.002 |pmc=2667997 |issn=0002-9297}}</ref>
* 2007, Member, [[American Academy of Arts and Sciences]]<ref name="AAAS">{{cite web |title=Haig H. Kazazian |url=https://www.amacad.org/person/haig-h-kazazian |website=American Academy of Arts & Sciences |access-date=6 February 2022 |language=en}}</ref>
* 2007, Member, [[American Academy of Arts and Sciences]]<ref name="AAAS">{{cite web |title=Haig H. Kazazian |url=https://www.amacad.org/person/haig-h-kazazian |website=American Academy of Arts & Sciences |access-date=6 February 2022 |language=en}}</ref>
* 1976, [[E. Mead Johnson Award]] for Pediatric Research, [[Society for Pediatric Research]]<ref name="Mead">{{cite web |title=Past Award Recipients - Society for Pediatric Research Award in honor of E. Mead Johnson |website=Society for Pediatric Research |url=https://www.societyforpediatricresearch.org/past-award-recipients/#toggle-id-4 |access-date=7 February 2022}}</ref>
* 1976, [[E. Mead Johnson Award]] for Pediatric Research, [[Society for Pediatric Research]]<ref name="Mead">{{cite web |title=Past Award Recipients - Society for Pediatric Research Award in honor of E. Mead Johnson |website=Society for Pediatric Research |url=https://www.societyforpediatricresearch.org/past-award-recipients/#toggle-id-4 |access-date=7 February 2022}}</ref>


== Papers==
== Papers==
* {{cite journal |last1=Kazazian |first1=H. H. |last2=Young |first2=W. J. |last3=Childs |first3=B. |title=X-Linked 6-Phosphogluconate Dehydrogenase in Drosophila : Subunit Associations |journal=Science |date=17 December 1965 |volume=150 |issue=3703 |pages=1601–1602 |url=https://www.science.org/doi/10.1126/science.150.3703.1601|doi=10.1126/science.150.3703.1601}}
* {{cite journal |last1=Kazazian |first1=H. H. |last2=Young |first2=W. J. |last3=Childs |first3=B. |title=X-Linked 6-Phosphogluconate Dehydrogenase in Drosophila : Subunit Associations |journal=Science |date=17 December 1965 |volume=150 |issue=3703 |pages=1601–1602 |url=https://www.science.org/doi/10.1126/science.150.3703.1601|doi=10.1126/science.150.3703.1601|pmid=5866658 |bibcode=1965Sci...150.1601K |s2cid=19571662 }}
* {{cite journal |last1=Phillips |first1=J. A. |last2=Snyder |first2=P. G. |last3=Kazazian |first3=H. H. |title=Ratios of α-to β-globin mRNA and regulation of globin synthesis in reticulocytes |journal=Nature |date=September 1977 |volume=269 |issue=5627 |pages=442–445 |doi=10.1038/269442a0 |url=https://www.nature.com/articles/269442a0}}
* {{cite journal |last1=Phillips |first1=J. A. |last2=Snyder |first2=P. G. |last3=Kazazian |first3=H. H. |title=Ratios of α-to β-globin mRNA and regulation of globin synthesis in reticulocytes |journal=Nature |date=September 1977 |volume=269 |issue=5627 |pages=442–445 |doi=10.1038/269442a0 |pmid=909594 |bibcode=1977Natur.269..442P |s2cid=4268291 |url=https://www.nature.com/articles/269442a0}}
* {{cite journal |last1=Antonarakis |first1=Stylianos E. |last2=Boehm |first2=Corinne D. |last3=Giardina |first3=Patricia J. V. |last4=Kazazian |first4=Haig H. |title=Nonrandom association of polymorphic restriction sites in the β-globin gene cluster |journal=Proceedings of the National Academy of Sciences of the United States of America |date=January 1982 |volume=79 |issue=1 |pages=137–141 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC345677/ |issn=0027-8424}}
* {{cite journal |last1=Antonarakis |first1=Stylianos E. |last2=Boehm |first2=Corinne D. |last3=Giardina |first3=Patricia J. V. |last4=Kazazian |first4=Haig H. |title=Nonrandom association of polymorphic restriction sites in the β-globin gene cluster |journal=Proceedings of the National Academy of Sciences of the United States of America |date=January 1982 |volume=79 |issue=1 |pages=137–141 |doi=10.1073/pnas.79.1.137 |pmid=6275383 |pmc=345677 |bibcode=1982PNAS...79..137A |issn=0027-8424|doi-access=free }}
* {{cite journal |last1=Orkin |first1=Stuart H. |last2=Kazazian |first2=Haig H. |last3=Antonarakis |first3=Stylianos E. |last4=Goff |first4=Sabra C. |last5=Boehm |first5=Corinne D. |last6=Sexton |first6=Julianne P. |last7=Waber |first7=Pamela G. |last8=Giardina |first8=Patricia J. V. |title=Linkage of β-thalassaemia mutations and β-globin gene polymorphisms with DNA polymorphisms in human β-globin gene cluster |journal=Nature |date=April 1982 |volume=296 |issue=5858 |pages=627–631 |doi=10.1038/296627a0}}
* {{cite journal |last1=Orkin |first1=Stuart H. |last2=Kazazian |first2=Haig H. |last3=Antonarakis |first3=Stylianos E. |last4=Goff |first4=Sabra C. |last5=Boehm |first5=Corinne D. |last6=Sexton |first6=Julianne P. |last7=Waber |first7=Pamela G. |last8=Giardina |first8=Patricia J. V. |title=Linkage of β-thalassaemia mutations and β-globin gene polymorphisms with DNA polymorphisms in human β-globin gene cluster |journal=Nature |date=April 1982 |volume=296 |issue=5858 |pages=627–631 |doi=10.1038/296627a0|pmid=6280057 |bibcode=1982Natur.296..627O |s2cid=4318868 }}
* {{cite journal |last1=Chakravarti |first1=A |last2=Buetow |first2=K H |last3=Antonarakis |first3=S E |last4=Waber |first4=P G |last5=Boehm |first5=C D |last6=Kazazian |first6=H H |title=Nonuniform recombination within the human beta-globin gene cluster. |journal=American Journal of Human Genetics |date=November 1984 |volume=36 |issue=6 |pages=1239–1258 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1684633/ |issn=0002-9297}}
* {{cite journal |last1=Chakravarti |first1=A |last2=Buetow |first2=K H |last3=Antonarakis |first3=S E |last4=Waber |first4=P G |last5=Boehm |first5=C D |last6=Kazazian |first6=H H |title=Nonuniform recombination within the human beta-globin gene cluster. |journal=American Journal of Human Genetics |date=November 1984 |volume=36 |issue=6 |pages=1239–1258 |pmid=6097112 |pmc=1684633 |issn=0002-9297}}
* {{cite journal |last1=Orkin |first1=Stuart H. |last2=Kazazian |first2=Haig H. |title=The mutation and polymorphism of the human β-globin gene and its surrounding DNA |journal=Annual Review of Genetics |date=1 December 1984 |volume=18 |issue=1 |pages=131–171 |doi=10.1146/annurev.ge.18.120184.001023 |url=https://doi.org/10.1146/annurev.ge.18.120184.001023 |issn=0066-4197}}
* {{cite journal |last1=Orkin |first1=Stuart H. |last2=Kazazian |first2=Haig H. |title=The mutation and polymorphism of the human β-globin gene and its surrounding DNA |journal=Annual Review of Genetics |date=1 December 1984 |volume=18 |issue=1 |pages=131–171 |doi=10.1146/annurev.ge.18.120184.001023 |pmid=6084979 |url=https://doi.org/10.1146/annurev.ge.18.120184.001023 |issn=0066-4197}}
* {{cite journal |last1=Francomano |first1=C A |last2=Kazazian |first2=H H |title=DNA Analysis in Genetic Disorders |journal=Annual Review of Medicine |date=1 February 1986 |volume=37 |issue=1 |pages=377–395 |doi=10.1146/annurev.me.37.020186.002113 |url=https://doi.org/10.1146/annurev.me.37.020186.002113 |issn=0066-4219}}
* {{cite journal |last1=Francomano |first1=C A |last2=Kazazian |first2=H H |title=DNA Analysis in Genetic Disorders |journal=Annual Review of Medicine |date=1 February 1986 |volume=37 |issue=1 |pages=377–395 |doi=10.1146/annurev.me.37.020186.002113 |pmid=3010808 |url=https://doi.org/10.1146/annurev.me.37.020186.002113 |issn=0066-4219}}
* {{cite journal |last1=Kazazian |first1=Haig H. |last2=Wong |first2=Corinne |last3=Youssoufian |first3=Hagop |last4=Scott |first4=Alan F. |last5=Phillips |first5=Deborah G. |last6=Antonarakis |first6=Stylianos E. |title=Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man |journal=Nature |date=March 1988 |volume=332 |issue=6160 |pages=164–166 |doi=10.1038/332164a0}}
* {{cite journal |last1=Kazazian |first1=Haig H. |last2=Wong |first2=Corinne |last3=Youssoufian |first3=Hagop |last4=Scott |first4=Alan F. |last5=Phillips |first5=Deborah G. |last6=Antonarakis |first6=Stylianos E. |title=Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man |journal=Nature |date=March 1988 |volume=332 |issue=6160 |pages=164–166 |doi=10.1038/332164a0|pmid=2831458 |bibcode=1988Natur.332..164K |s2cid=4259071 }}
* {{cite journal |last1=Dombroski |first1=Beth A. |last2=Mathias |first2=Stephen L. |last3=Nanthakumar |first3=Elizabeth |last4=Scott |first4=Alan F. |last5=Kazazian |first5=Haig H. |title=Isolation of an Active Human Transposable Element |journal=Science |date=20 December 1991 |volume=254 |issue=5039 |pages=1805–1808 |doi=10.1126/science.1662412}}
* {{cite journal |last1=Dombroski |first1=Beth A. |last2=Mathias |first2=Stephen L. |last3=Nanthakumar |first3=Elizabeth |last4=Scott |first4=Alan F. |last5=Kazazian |first5=Haig H. |title=Isolation of an Active Human Transposable Element |journal=Science |date=20 December 1991 |volume=254 |issue=5039 |pages=1805–1808 |doi=10.1126/science.1662412|pmid=1662412 |bibcode=1991Sci...254.1805D }}
* {{cite journal |last1=Bi |first1=L. |last2=Lawler |first2=A.M. |last3=Antonarakis |first3=S.E. |last4=High |first4=K.A. |last5=Gearhart |first5=J.D. |last6=Kazazian |first6=H.H. |title=Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A |journal=Nature Genetics |date=May 1995 |volume=10 |issue=1 |pages=119–121 |doi=10.1038/ng0595-119}}
* {{cite journal |last1=Bi |first1=L. |last2=Lawler |first2=A.M. |last3=Antonarakis |first3=S.E. |last4=High |first4=K.A. |last5=Gearhart |first5=J.D. |last6=Kazazian |first6=H.H. |title=Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A |journal=Nature Genetics |date=May 1995 |volume=10 |issue=1 |pages=119–121 |doi=10.1038/ng0595-119|pmid=7647782 |s2cid=27366245 }}
* {{cite journal |last1=Moran |first1=John V |last2=Holmes |first2=Susan E |last3=Naas |first3=Thierry P |last4=DeBerardinis |first4=Ralph J |last5=Boeke |first5=Jef D |last6=Kazazian |first6=Haig H |title=High Frequency Retrotransposition in Cultured Mammalian Cells |journal=Cell |date=November 1996 |volume=87 |issue=5 |pages=917–927 |doi=10.1016/s0092-8674(00)81998-4}}
* {{cite journal |last1=Moran |first1=John V |last2=Holmes |first2=Susan E |last3=Naas |first3=Thierry P |last4=DeBerardinis |first4=Ralph J |last5=Boeke |first5=Jef D |last6=Kazazian |first6=Haig H |title=High Frequency Retrotransposition in Cultured Mammalian Cells |journal=Cell |date=November 1996 |volume=87 |issue=5 |pages=917–927 |doi=10.1016/s0092-8674(00)81998-4|pmid=8945518 |s2cid=260983 |doi-access=free }}
* {{cite journal |last1=Moran |first1=John V. |last2=DeBerardinis |first2=Ralph J. |last3=Kazazian |first3=Haig H. |title=Exon Shuffling by L1 Retrotransposition |journal=Science |date=5 March 1999 |volume=283 |issue=5407 |pages=1530–1534 |doi=10.1126/science.283.5407.1530}}
* {{cite journal |last1=Moran |first1=John V. |last2=DeBerardinis |first2=Ralph J. |last3=Kazazian |first3=Haig H. |title=Exon Shuffling by L1 Retrotransposition |journal=Science |date=5 March 1999 |volume=283 |issue=5407 |pages=1530–1534 |doi=10.1126/science.283.5407.1530|pmid=10066175 |bibcode=1999Sci...283.1530M }}
* {{cite journal |last1=Kazazian |first1=Haig H. |title=L1 Retrotransposons Shape the Mammalian Genome |journal=Science |date=18 August 2000 |volume=289 |issue=5482 |pages=1152–1153 |doi=10.1126/science.289.5482.1152}}
* {{cite journal |last1=Kazazian |first1=Haig H. |title=L1 Retrotransposons Shape the Mammalian Genome |journal=Science |date=18 August 2000 |volume=289 |issue=5482 |pages=1152–1153 |doi=10.1126/science.289.5482.1152|pmid=10970230 |s2cid=83267969 }}
* {{cite journal |last1=Ostertag |first1=Eric M. |last2=Kazazian Jr |first2=Haig H. |title=Biology of Mammalian L1 Retrotransposons |journal=Annual Review of Genetics |date=1 December 2001 |volume=35 |issue=1 |pages=501–538 |doi=10.1146/annurev.genet.35.102401.091032 |url=https://doi.org/10.1146/annurev.genet.35.102401.091032 |issn=0066-4197}}
* {{cite journal |last1=Ostertag |first1=Eric M. |last2=Kazazian Jr |first2=Haig H. |title=Biology of Mammalian L1 Retrotransposons |journal=Annual Review of Genetics |date=1 December 2001 |volume=35 |issue=1 |pages=501–538 |doi=10.1146/annurev.genet.35.102401.091032 |pmid=11700292 |url=https://doi.org/10.1146/annurev.genet.35.102401.091032 |issn=0066-4197}}
* {{cite journal |last1=Ostertag |first1=Eric M. |last2=DeBerardinis |first2=Ralph J. |last3=Goodier |first3=John L. |last4=Zhang |first4=Yue |last5=Yang |first5=Nuo |last6=Gerton |first6=George L. |last7=Kazazian |first7=Haig H. |title=A mouse model of human L1 retrotransposition |journal=Nature Genetics |date=December 2002 |volume=32 |issue=4 |pages=655–660 |doi=10.1038/ng1022}}
* {{cite journal |last1=Ostertag |first1=Eric M. |last2=DeBerardinis |first2=Ralph J. |last3=Goodier |first3=John L. |last4=Zhang |first4=Yue |last5=Yang |first5=Nuo |last6=Gerton |first6=George L. |last7=Kazazian |first7=Haig H. |title=A mouse model of human L1 retrotransposition |journal=Nature Genetics |date=December 2002 |volume=32 |issue=4 |pages=655–660 |doi=10.1038/ng1022|pmid=12415270 |s2cid=22004980 }}
* {{cite journal |last1=Hancks |first1=Dustin C. |last2=Goodier |first2=John L. |last3=Mandal |first3=Prabhat K. |last4=Cheung |first4=Ling E. |last5=Kazazian |first5=Haig H. |title=Retrotransposition of marked SVA elements by human L1s in cultured cells |journal=Human Molecular Genetics |date=1 September 2011 |volume=20 |issue=17 |pages=3386–3400 |doi=10.1093/hmg/ddr245 |url=https://doi.org/10.1093/hmg/ddr245}}
* {{cite journal |last1=Hancks |first1=Dustin C. |last2=Goodier |first2=John L. |last3=Mandal |first3=Prabhat K. |last4=Cheung |first4=Ling E. |last5=Kazazian |first5=Haig H. |title=Retrotransposition of marked SVA elements by human L1s in cultured cells |journal=Human Molecular Genetics |date=1 September 2011 |volume=20 |issue=17 |pages=3386–3400 |doi=10.1093/hmg/ddr245 |pmid=21636526 |pmc=3153304 |url=https://doi.org/10.1093/hmg/ddr245}}


==References==
==References==
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Latest revision as of 23:02, 23 March 2024

Haig Kazazian
Born
Haig Hagop Kazazian Jr.

(1937-07-30)July 30, 1937[1]
Toledo, Ohio
DiedJanuary 20, 2022(2022-01-20) (aged 84)
Towson, Maryland
Alma materDartmouth College, Johns Hopkins University School of Medicine
Scientific career
FieldsGenetics
InstitutionsJohns Hopkins University School of Medicine, University of Pennsylvania

Haig Hagop Kazazian Jr. (July 30, 1937 – January 19/20, 2022) was an American professor in the Department of Genetic Medicine at Johns Hopkins University School of Medicine in Baltimore, Maryland.[2] Kazazian was an elected member of the National Academy of Sciences[3] and the American Academy of Arts and Sciences.[4]

Kazazian determined the molecular basis of single-gene genetic disorders such as hemoglobinopathies and hemophilia and introduced prenatal diagnosis for such disorders. His group was the first to identify a disease-causing mutation resulting from jumping genes in humans.[5] After this discovery, he focused on basic research into LINE retrotransposition in humans and its implications for disease.[6]

Early life and education[edit]

Haig Hagop Kazazian Jr.'s Armenian father was from Kayseri, Turkey. He was sent to the Ras el Ain concentration camp in Syria as part of the Armenian genocide, but escaped in 1918 and arrived in the U.S. in 1923.[7][8][9] Kazazian's mother, Hermine,[10] left Istanbul and arrived in the U.S. in 1920.[7][8][9] They married on January 1, 1929.[7]

Haig Jr. was born in Toledo, Ohio,[8] on July 30, 1937.[1] He grew up speaking Armenian, Turkish and English.[8] He attended Dartmouth College, receiving his A.B. degree from Dartmouth College in 1959, followed by a two-year program at Dartmouth Medical School. He completed his M.D. degree at Johns Hopkins University School of Medicine[11] in 1962, and interned in pediatrics at the University of Minnesota.[8]

Career[edit]

Kazazian returned to Baltimore, Maryland as a postdoctoral fellow, studying the genetics of fruit flies and X chromosome inactivation with Barton Childs at Johns Hopkins (1964–1966)[12][8][9] In 1966, he joined Harvey Itano at the National Institutes of Health,[11] working as a staff associate for the US Public Health Service.[7] In Itano's labotory, Kazazian worked on hemoglobin regulation.[9]

Kazazian joined the faculty at Johns Hopkins in 1969.[2] He became a full professor, heading the Pediatric Genetics Unit, in 1977.[11] In 1979,[7] he established one of the first DNA diagnostic laboratories, providing molecular detection facilities for identifying monogenic disorders. He introduced prenatal diagnosis for hemoglobin disorders.[2] In 1988, Kazazian became Director of the Center for Medical Genetics at Johns Hopkins.[11] From 1988 to 1994, he and Maxine Singer at the National Institutes of Health (NIH) held joint quarterly lab meetings, sharing their knowledge of the biochemistry and genetics.[13]

Kazazian and Richard Cotton were founding co-editors of the journal Human Mutation, which appeared in 1992.[14] Kazazian became a co-editor of the journal Mobile DNA in 2015.[15]

In 1994, he became Chair of the Department of Genetics at the University of Pennsylvania School of Medicine, holding the position until 2006.[12] He remained at the University of Pennsylvaniaf as the Seymour Gray Professor of Molecular Medicine in Genetics from 2006 to 2010.[11]

In 1999, Kazazian and Arupa Ganguly joined the plaintiffs for Association for Molecular Pathology v. Myriad Genetics, Inc.,[2][16] after they were served with a cease-and-desist letter demanding that they stop breast cancer screenings for the BRCA1 and BRCA2 genes.[7] In a unanimous ruling in 2013, the Supreme Court ruled that companies cannot patent parts of naturally occurring human genes. The Court stated that "a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but manmade cDNA is patent eligible because it is not naturally occurring."[17][18][19] In July 2010, Kazazian returned to Johns Hopkins, holding the position of a Professor in the Institute of Genetic Medicine.[11] He closed his laboratory there in 2020.[3]

His book Mobile DNA: Finding Treasure in Junk (2011) gives an overview of research on transposable elements. It does a "remarkable job" of discussing early contributors, the development of computational biology, and the field of mobile DNA and retrotransposable elements.[20] Although the initial chapters of background information on the field have been criticized as less interesting than later and more personal chapters, the account is credited with vividly illustrating "both the destructive and constructive facets of transposition in the genome".[21]

Kazazian died on January 19[2] or 20, 2022 in Towson, Maryland.[12]

Research[edit]

Kazazian made important contributions to human genetics through his research into DNA haplotypes and the molecular basis of beta thalassemia and through his exploration of retrotransposons (jumping genes).[7]

Much of his early research focused on the regulation of hemoglobin synthesis and its implications for the human blood disorder β-thalassemia.[9] Using information on β-globin DNA polymorphisms from Stylianos Antonarakis and others, Kazazian helped develop methods for prenatal diagnosis of sickle cell anemia. Coining the term haplotypes for certain types of polymorphisms, Kazazian collaborated with Stuart Orkin to characterize the mutations causing beta-thalassemia.[9][2] He used haplotypes to classify β-thalassemia mutations in patients from around the world and to prenatally identify β-thalassemia.[12]

In the 1980s, Kazazian began to study the factor 8 blood-clotting gene, which was known to be defective in hemophilia A. Lab member Hagop Youssoufian found a long interspersed nuclear element (LINE) insertion, a mobile DNA element or transposon colloquially known as a “jumping gene”. Jumping genes were discovered in maize by Barbara McClintock.[9] The Kazazian lab was the first to discover a jumping gene in humans, and to demonstrate that a transposable element caused disease in man via insertional mutagenesis.[4][5][2] Kazazian expanded this work to mouse models, providing evidence that active retrotransposons occur in other mammals.[4]

Since then Kazazian has focused on basic research into LINE retrotransposition in humans, and the role of jumping genes in human disease. Retrotransposons copy and insert themselves into new locations in the genome.[6] As a postdoctoral fellow with Kazazian, John Moran developed a cell culture assay to detect retrotransposition. They determined that the average human genome has 80–100 active LINE-1 (L1) retrotransposons, a handful of which are very active.[9][6][22] In addition to understanding diseases, studying L1 insertions enables researchers to learn about human diversity.[6]

Kazazian's studies with rodents suggest that retrotransposition tends to occur during early embryonic development.[9] Kazazian found that retrotransposon mobility causes shuffling of exons and their flanking sequences, a discovery with important implications for the understanding of evolution.[4]

Kazazian investigated the possibility that LINE-1 jumping genes play a role in cancer. He and others have observed instances of new insertions of jumping genes in some cancers, but he could not determine whether LINE-1 genes drive cancer development or are a side effect of cancer.[23]

Awards[edit]

Papers[edit]

References[edit]

  1. ^ a b "Kazazian, Haig H., Jr., 1937-". Library of Congress Authorities. Retrieved February 7, 2022.
  2. ^ a b c d e f g Wasta, Vanessa; Butch, Rachel (February 2, 2022). "Haig Kazazian, pioneer in genetic medicine, dies at 84". The Hub. Retrieved February 6, 2022.
  3. ^ a b c "Haig H. Kazazian". National Academy of Sciences. Retrieved February 7, 2022.
  4. ^ a b c d e "Haig H. Kazazian". American Academy of Arts & Sciences. Retrieved February 6, 2022.
  5. ^ a b Singer, Maxine F. (1994). "From Genomic Junk to Human Disease". Proceedings of the American Philosophical Society. 138 (1): 11–24. ISSN 0003-049X. JSTOR 986702. Retrieved February 7, 2022.
  6. ^ a b c d "Johns Hopkins Researchers Capture Jumping Genes". Johns Hopkins Medicine. February 4, 2011. Retrieved February 6, 2022.
  7. ^ a b c d e f g Kazazian, Haig H. (August 31, 2021). "A Long, Fulfilling Career in Human Genetics". Annual Review of Genomics and Human Genetics. 22 (1): 27–53. doi:10.1146/annurev-genom-111620-095614. ISSN 1527-8204. PMID 33945751. S2CID 233744364.
  8. ^ a b c d e f g Antonarakis, Stylianos E. (February 13, 2009). "William Allan Award Introduction: Haig H. Kazazian, Jr". American Journal of Human Genetics. 84 (2): 103–104. doi:10.1016/j.ajhg.2009.01.002. ISSN 0002-9297. PMC 2667997.
  9. ^ a b c d e f g h i j Azar, Beth (December 22, 2020). "Profile of Haig H. Kazazian Jr". Proceedings of the National Academy of Sciences. 117 (51): 32185–32188. Bibcode:2020PNAS..11732185A. doi:10.1073/pnas.2023398117. ISSN 0027-8424. PMC 7768710. PMID 33273116.
  10. ^ "Hermine A. Kazazian Obituary". The Detroit News. 2007. Retrieved February 7, 2022.
  11. ^ a b c d e f "Haig H. Kazazian". InformIT. Retrieved February 5, 2022.
  12. ^ a b c d Rader, Daniel J. (January 25, 2022). "Announcement from Dr. Rader: Death of Haig H Kazazian, Jr, MD". Penn Genetics. Retrieved February 7, 2022.
  13. ^ Kazazian, Haig H. (March 18, 2011). Mobile DNA: Finding Treasure in Junk. Upper Saddle River, NJ: FT Press. ISBN 978-0-13-257525-6. Retrieved February 7, 2022.
  14. ^ "Infectious Enthusiasm! Larger than Life! That Laugh! That Smile! In Loving Memory of Richard G.H. (Dick) Cotton". Human Mutation. 37 (6): 598–615. 2016. doi:10.1002/humu.22990. PMID 27030029. S2CID 205923182.
  15. ^ Rose, Sam (April 17, 2015). "Mobile DNA welcomes new Editors-in-Chief, Marlene Belfort and Haig Kazazian". On Biology. Retrieved February 7, 2022.
  16. ^ Butanis, Benjamin. "Supreme Court Rules on Gene Patent Case". Johns Hopkins Medicine. Retrieved February 6, 2022.
  17. ^ Goldstein, Tom (June 13, 2013). "Details on Association for Molecular Pathology v. Myriad Genetics, Inc". SCOTUSblog. Retrieved February 6, 2022.
  18. ^ Brandom, Russell (June 14, 2013). "After Supreme Court ruling, don't count out gene patenting quite yet". The Verge. Retrieved February 6, 2022.
  19. ^ Marbella, Jean (June 13, 2013). "Ban on patenting DNA cheers researchers". The Baltimore Sun. Retrieved February 6, 2022.
  20. ^ Batzer, Mark A. (July 11, 2013). "Mobile DNA: Finding Treasure in Junk". American Journal of Human Genetics. 93 (1): 5. doi:10.1016/j.ajhg.2013.06.001. ISSN 0002-9297. PMC 3710766.
  21. ^ Feschotte, Cédric (October 3, 2012). "Review of Mobile DNA - finding treasure in junk by Haig H Kazazian". Mobile DNA. 3 (1): 16. doi:10.1186/1759-8753-3-16. ISSN 1759-8753. PMC 3517452. S2CID 1024114.
  22. ^ Ishak, Charles A.; De Carvalho, Daniel D. (March 9, 2020). "Reactivation of Endogenous Retroelements in Cancer Development and Therapy". Annual Review of Cancer Biology. 4 (1): 159–176. doi:10.1146/annurev-cancerbio-030419-033525. ISSN 2472-3428. S2CID 213919601.
  23. ^ Ives, James (October 6, 2015). "Jumping genes: a marker for early cancer diagnosis? An interview with Dr Kazazian". News-Medical.net. Retrieved February 7, 2022.
  24. ^ "Past Award Recipients - Society for Pediatric Research Award in honor of E. Mead Johnson". Society for Pediatric Research. Retrieved February 7, 2022.
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