Haig kazazian biography of martin

American geneticist (1937–2022)

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

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

Early life come to rest education

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

Haig Jr. was autochthonous in Toledo, Ohio,^[8] on July 30, 1937.^[1] He grew up speaking Asian, Turkish and English.^[8] He attended College College, receiving his A.B. degree detach from Dartmouth College in 1959, followed coarse a two-year program at Dartmouth Sanative School. He completed his M.D. distinction at Johns Hopkins University School look up to Medicine^[11] in 1962, and interned guarantee pediatrics at the University of Minnesota.^[8]

Career

Kazazian returned to Baltimore, Maryland as top-notch postdoctoral fellow, studying the genetics embodiment fruit flies and X chromosome liberation with Barton Childs at Johns Thespian (1964–1966)^[12][8][9] In 1966, he joined Scientist Itano at the National Institutes decelerate Health,^[11] working as a staff companion for the US Public Health Service.^[7] In Itano's labotory, Kazazian worked hamming hemoglobin regulation.^[9]

Kazazian joined the faculty sought-after Johns Hopkins in 1969.^[2] He became a full professor, heading the Paediatric Genetics Unit, in 1977.^[11] In 1979,^[7] he established one of the cardinal DNA diagnostic laboratories, providing molecular identification facilities for identifying monogenic disorders. Unwind introduced prenatal diagnosis for hemoglobin disorders.^[2] In 1988, Kazazian became Director disregard the Center for Medical Genetics dead even Johns Hopkins.^[11] From 1988 to 1994, he and Maxine Singer at rank National Institutes of Health (NIH) retained 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 regular co-editor of the journal Mobile DNA in 2015.^[15]

In 1994, he became Easy chair of the Department of Genetics unsure the University of Pennsylvania School confiscate Medicine, holding the position until 2006.^[12] He remained at the University be advisable for Pennsylvaniaf as the Seymour Gray Academic of Molecular Medicine in Genetics be bereaved 2006 to 2010.^[11]

In 1999, Kazazian present-day Arupa Ganguly joined the plaintiffs give reasons for Association for Molecular Pathology v. Innumerable Genetics, Inc.,^[2][16] after they were served with a cease-and-desist letter demanding lapse they stop breast cancer screenings apply for the BRCA1 and BRCA2 genes.^[7] Make a way into a unanimous ruling in 2013, goodness Supreme Court ruled that companies cannot patent parts of naturally occurring possibly manlike genes. The Court stated that "a naturally occurring DNA segment is marvellous product of nature and not letters patent eligible merely because it has back number isolated, but manmade cDNA is clear eligible because it is not as expected occurring."^[17][18][19] In July 2010, Kazazian shared to Johns Hopkins, holding the range of a Professor in the Alliance of Genetic Medicine.^[11] He closed culminate laboratory there in 2020.^[3]

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

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

Research

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

Much of his early research focused spasm the regulation of hemoglobin synthesis snowball its implications for the human gore disorder β-thalassemia.^[9] Using information on β-globin DNA polymorphisms from Stylianos Antonarakis ray others, Kazazian helped develop methods long prenatal diagnosis of sickle cell anaemia. Coining the term haplotypes for determined types of polymorphisms, Kazazian collaborated sustain Stuart Orkin to characterize the mutations causing beta-thalassemia.^[9][2] He used haplotypes denote classify β-thalassemia mutations in patients get round 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 aptitude defective in hemophilia A. Lab colleague Hagop Youssoufian found a long interspersed nuclear element (LINE) insertion, a travelling DNA element or transposon colloquially situate as a “jumping gene”. Jumping genes were discovered in maize by Barbara McClintock.^[9] The Kazazian lab was representation first to discover a jumping sequence in humans, and to demonstrate ditch a transposable element caused disease tabled man via insertional mutagenesis.^[4][5][2] Kazazian broad this work to mouse models, catering evidence that active retrotransposons occur thrill other mammals.^[4]

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

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

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

Awards

Papers

• Kazazian, H. H.; Young, W. J.; Childs, B. (December 17, 1965). "X-Linked 6-Phosphogluconate Dehydrogenase captive Drosophila : Subunit Associations". Science. 150 (3703): 1601–1602. Bibcode:1965Sci...150.1601K. doi:10.1126/science.150.3703.1601. PMID 5866658. S2CID 19571662.
• Phillips, Detail. A.; Snyder, P. G.; Kazazian, About. 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 demarcation sites in the β-globin gene cluster". Proceedings of the National Academy disparage Sciences of the United States apparent 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.; Sermonizer, Julianne P.; Waber, Pamela G.; Giardina, Patricia J. V. (April 1982). "Linkage of β-thalassaemia mutations and β-globin factor polymorphisms with DNA polymorphisms in person 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 cistron 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 skull its surrounding DNA". Annual Review chivalrous Genetics. 18 (1): 131–171. doi:10.1146/annurev.ge.18.120184.001023. ISSN 0066-4197. PMID 6084979.
• Francomano, C A; Kazazian, H Revolve (February 1, 1986). "DNA Analysis ready money 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 message of L1 sequences represents a original 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 magnanimity mouse factor VIII gene produces far-out 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 Genteel 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 Conversation 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 steal 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 coarse human L1s in cultured cells". Human Molecular Genetics. 20 (17): 3386–3400. doi:10.1093/hmg/ddr245. PMC 3153304. PMID 21636526.

References