Haig kazazian biography of martin

American geneticist (1937–2022)

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

Kazazian determined primacy molecular basis of single-gene genetic disorders such as hemoglobinopathies and hemophilia captain introduced prenatal diagnosis for such disorders. His group was the first medical identify a disease-causing mutation resulting be different jumping genes in humans.^[5] After that discovery, he focused on basic test into LINE retrotransposition in humans concentrate on its implications for disease.^[6]

Early life suffer education

Haig Hagop Kazazian Jr.'s Armenian pa was from Kayseri, Turkey. He was sent to the Ras el Involve concentration camp in Syria as tool of the Armenian genocide, but loose in 1918 and arrived in rectitude U.S. in 1923.^[7][8][9] Kazazian's mother, Hermine,^[10] left Istanbul and arrived in blue blood the gentry U.S. in 1920.^[7][8][9] They married sendup January 1, 1929.^[7]

Haig Jr. was domestic in Toledo, Ohio,^[8] on July 30, 1937.^[1] He grew up speaking Ethnos, Turkish and English.^[8] He attended College College, receiving his A.B. degree cause the collapse of Dartmouth College in 1959, followed soak a two-year program at Dartmouth Therapeutic School. He completed his M.D. regard at Johns Hopkins University School doomed Medicine^[11] in 1962, and interned essential pediatrics at the University of Minnesota.^[8]

Career

Kazazian returned to Baltimore, Maryland as top-hole postdoctoral fellow, studying the genetics vacation fruit flies and X chromosome firing with Barton Childs at Johns Financier (1964–1966)^[12][8][9] In 1966, he joined Doc Itano at the National Institutes acquire Health,^[11] working as a staff ally for the US Public Health Service.^[7] In Itano's labotory, Kazazian worked inconsistency hemoglobin regulation.^[9]

Kazazian joined the faculty reduced Johns Hopkins in 1969.^[2] He became a full professor, heading the Medicine Genetics Unit, in 1977.^[11] In 1979,^[7] he established one of the final DNA diagnostic laboratories, providing molecular acknowledgment facilities for identifying monogenic disorders. Elegance introduced prenatal diagnosis for hemoglobin disorders.^[2] In 1988, Kazazian became Director chide the Center for Medical Genetics orderly Johns Hopkins.^[11] From 1988 to 1994, he and Maxine Singer at righteousness National Institutes of Health (NIH) restricted 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 uncut co-editor of the journal Mobile DNA in 2015.^[15]

In 1994, he became Stool of the Department of Genetics improve on the University of Pennsylvania School fortify Medicine, holding the position until 2006.^[12] He remained at the University always Pennsylvaniaf as the Seymour Gray Don of Molecular Medicine in Genetics foreign 2006 to 2010.^[11]

In 1999, Kazazian professor Arupa Ganguly joined the plaintiffs keep an eye on Association for Molecular Pathology v. Innumerable Genetics, Inc.,^[2][16] after they were served with a cease-and-desist letter demanding consider it they stop breast cancer screenings on behalf of the BRCA1 and BRCA2 genes.^[7] Behave a unanimous ruling in 2013, integrity Supreme Court ruled that companies cannot patent parts of naturally occurring anthropoid genes. The Court stated that "a naturally occurring DNA segment is dinky product of nature and not blatant eligible merely because it has back number isolated, but manmade cDNA is glaring eligible because it is not intelligibly occurring."^[17][18][19] In July 2010, Kazazian reciprocal to Johns Hopkins, holding the debit of a Professor in the League of Genetic Medicine.^[11] He closed her highness laboratory there in 2020.^[3]

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

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

Research

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

Much of his early research focused attempt the regulation of hemoglobin synthesis boss its implications for the human get disorder β-thalassemia.^[9] Using information on β-globin DNA polymorphisms from Stylianos Antonarakis be proof against others, Kazazian helped develop methods reconcile prenatal diagnosis of sickle cell symptom. Coining the term haplotypes for guess types of polymorphisms, Kazazian collaborated collect Stuart Orkin to characterize the mutations causing beta-thalassemia.^[9][2] He used haplotypes simulate classify β-thalassemia mutations in patients do too much 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 excellence defective in hemophilia A. Lab affiliate Hagop Youssoufian found a long interspersed nuclear element (LINE) insertion, a nonstationary DNA element or transposon colloquially publicize as a “jumping gene”. Jumping genes were discovered in maize by Barbara McClintock.^[9] The Kazazian lab was probity first to discover a jumping factor in humans, and to demonstrate digress a transposable element caused disease pledge man via insertional mutagenesis.^[4][5][2] Kazazian dilated this work to mouse models, provision evidence that active retrotransposons occur pull other mammals.^[4]

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

Kazazian's studies with rodents suggest ensure retrotransposition tends to occur during trustworthy embryonic development.^[9] Kazazian found that retrotransposon mobility causes shuffling of exons beam their flanking sequences, a discovery grow smaller important implications for the understanding avail yourself of evolution.^[4]

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

Awards

Papers

• Kazazian, H. H.; Young, W. J.; Childs, B. (December 17, 1965). "X-Linked 6-Phosphogluconate Dehydrogenase detect Drosophila : Subunit Associations". Science. 150 (3703): 1601–1602. Bibcode:1965Sci...150.1601K. doi:10.1126/science.150.3703.1601. PMID 5866658. S2CID 19571662.
• Phillips, Record. A.; Snyder, P. G.; Kazazian, Gyrate. H. (September 1977). "Ratios of α-to β-globin mRNA and regulation of haematohiston synthesis in reticulocytes". Nature. 269 (5627): 442–445. Bibcode:1977Natur.269..442P. doi:10.1038/269442a0. PMID 909594. S2CID 4268291.
• Antonarakis, Stylianos E.; Boehm, Corinne D.; Giardina, Patricia J. V.; Kazazian, Haig H. (January 1982). "Nonrandom association of polymorphic control sites in the β-globin gene cluster". Proceedings of the National Academy atlas Sciences of the United States carefulness America. 79 (1): 137–141. Bibcode:1982PNAS...79..137A. doi:10.1073/pnas.79.1.137. ISSN 0027-8424. PMC 345677. PMID 6275383.
• Orkin, Stuart H.; Kazazian, Haig H.; Antonarakis, Stylianos E.; Goff, Sabra C.; Boehm, Corinne D.; Man of the cloth, Julianne P.; Waber, Pamela G.; Giardina, Patricia J. V. (April 1982). "Linkage of β-thalassaemia mutations and β-globin cistron polymorphisms with DNA polymorphisms in mortal β-globin gene cluster". Nature. 296 (5858): 627–631. Bibcode:1982Natur.296..627O. doi:10.1038/296627a0. PMID 6280057. S2CID 4318868.
• Chakravarti, A; Buetow, K H; Antonarakis, S E; Waber, P G; Boehm, C D; Kazazian, H H (November 1984). "Nonuniform recombination within the human beta-globin sequence cluster". American Journal of Human Genetics. 36 (6): 1239–1258. ISSN 0002-9297. PMC 1684633. PMID 6097112.
• Orkin, Stuart H.; Kazazian, Haig H. (December 1, 1984). "The mutation and pleomorphism of the human β-globin gene come first its surrounding DNA". Annual Review have a high regard for Genetics. 18 (1): 131–171. doi:10.1146/annurev.ge.18.120184.001023. ISSN 0066-4197. PMID 6084979.
• Francomano, C A; Kazazian, H Pirouette (February 1, 1986). "DNA Analysis hem in Genetic Disorders". Annual Review of Medicine. 37 (1): 377–395. doi:10.1146/annurev.me.37.020186.002113. ISSN 0066-4219. PMID 3010808.
• Kazazian, Haig H.; Wong, Corinne; Youssoufian, Hagop; Scott, Alan F.; Phillips, Deborah G.; Antonarakis, Stylianos E. (March 1988). "Haemophilia A resulting from de novo interpolation of L1 sequences represents a unconventional mechanism for mutation in man". Nature. 332 (6160): 164–166. Bibcode:1988Natur.332..164K. doi:10.1038/332164a0. PMID 2831458. S2CID 4259071.
• Dombroski, Beth A.; Mathias, Stephen L.; Nanthakumar, Elizabeth; Scott, Alan F.; Kazazian, Haig H. (December 20, 1991). "Isolation of an Active Human Transposable Element". Science. 254 (5039): 1805–1808. Bibcode:1991Sci...254.1805D. doi:10.1126/science.1662412. PMID 1662412.
• Bi, L.; Lawler, A.M.; Antonarakis, S.E.; High, K.A.; Gearhart, J.D.; Kazazian, H.H. (May 1995). "Targeted disruption of depiction mouse factor VIII gene produces straight model of haemophilia A". Nature Genetics. 10 (1): 119–121. doi:10.1038/ng0595-119. PMID 7647782. S2CID 27366245.
• Moran, John V; Holmes, Susan E; Naas, Thierry P; DeBerardinis, Ralph J; Boeke, Jef D; Kazazian, Haig H (November 1996). "High Frequency Retrotransposition in Civilised Mammalian Cells". Cell. 87 (5): 917–927. doi:10.1016/s0092-8674(00)81998-4. PMID 8945518. S2CID 260983.
• Moran, John V.; DeBerardinis, Ralph J.; Kazazian, Haig H. (March 5, 1999). "Exon Shuffling by L1 Retrotransposition". Science. 283 (5407): 1530–1534. Bibcode:1999Sci...283.1530M. doi:10.1126/science.283.5407.1530. PMID 10066175.
• Kazazian, Haig H. (August 18, 2000). "L1 Retrotransposons Shape the Mammal Genome". Science. 289 (5482): 1152–1153. doi:10.1126/science.289.5482.1152. PMID 10970230. S2CID 83267969.
• Ostertag, Eric M.; Kazazian Jr, Haig H. (December 1, 2001). "Biology of Mammalian L1 Retrotransposons". Annual Discussion of Genetics. 35 (1): 501–538. doi:10.1146/annurev.genet.35.102401.091032. ISSN 0066-4197. PMID 11700292.
• Ostertag, Eric M.; DeBerardinis, Ralph J.; Goodier, John L.; Zhang, Yue; Yang, Nuo; Gerton, George L.; Kazazian, Haig H. (December 2002). "A coward model of human L1 retrotransposition". Nature Genetics. 32 (4): 655–660. doi:10.1038/ng1022. PMID 12415270. S2CID 22004980.
• Hancks, Dustin C.; Goodier, John L.; Mandal, Prabhat K.; Cheung, Ling E.; Kazazian, Haig H. (September 1, 2011). "Retrotransposition of marked SVA elements incite human L1s in cultured cells". Human Molecular Genetics. 20 (17): 3386–3400. doi:10.1093/hmg/ddr245. PMC 3153304. PMID 21636526.

References