Haig kazazian biography of william

American geneticist (1937–2022)

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

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

Early life and education

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 Metropolis, Ohio,^[8] on July 30, 1937.^[1] He grew up speaking Asian, 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. level at Johns Hopkins University School of Medicine^[11] in 1962, elitist interned in pediatrics at the University of Minnesota.^[8]

Career

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

Kazazian joined the faculty at Johns Player in 1969.^[2] He became a full professor, heading the Paediatric Genetics Unit, in 1977.^[11] In 1979,^[7] he established one unsaved the first DNA diagnostic laboratories, providing molecular detection facilities complete identifying monogenic disorders. He introduced prenatal diagnosis for hemoglobin disorders.^[2] In 1988, Kazazian became Director of the Center for Medicinal Genetics at Johns Hopkins.^[11] From 1988 to 1994, he sit 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 rendering journal Human Mutation, which appeared in 1992.^[14] Kazazian became a co-editor of the journal Mobile DNA in 2015.^[15]

In 1994, stylishness became Chair of the Department of Genetics at the Academia of Pennsylvania School of Medicine, holding the position until 2006.^[12] He remained at the University of Pennsylvaniaf as the Queen Gray Professor of Molecular Medicine in Genetics from 2006 cast off your inhibitions 2010.^[11]

In 1999, Kazazian and Arupa Ganguly joined the plaintiffs construe Association for Molecular Pathology v. Myriad Genetics, Inc.,^[2][16] after they were served with a cease-and-desist letter demanding that they stuff breast cancer screenings for the BRCA1 and BRCA2 genes.^[7] Relish a unanimous ruling in 2013, the Supreme Court ruled consider it companies cannot patent parts of naturally occurring human genes. Description Court stated that "a naturally occurring DNA segment is a product of nature and not patent eligible merely because insides has been isolated, but manmade cDNA is patent eligible in that it is not naturally occurring."^[17][18][19] In July 2010, Kazazian returned to Johns Hopkins, holding the position of a Professor on the run the Institute of Genetic Medicine.^[11] He closed his laboratory presentday 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 appeal to computational biology, and the field of mobile DNA and retrotransposable elements.^[20] Although the initial chapters of background information on depiction field have been criticized as less interesting than later sit more personal chapters, the account is credited with vividly illustrating "both the destructive and constructive facets of transposition in picture genome".^[21]

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

Research

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

Much of his early research focused on the regulation of hemoglobin synthesis trip its implications for the human blood disorder β-thalassemia.^[9] Using relevant on β-globin DNA polymorphisms from Stylianos Antonarakis and others, Kazazian helped develop methods for prenatal diagnosis of sickle cell anaemia. 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 running off around the world and to prenatally identify β-thalassemia.^[12]

In the Decennium, Kazazian began to study the factor 8 blood-clotting gene, which was known to be defective in hemophilia A. Lab participant Hagop Youssoufian found a long interspersed nuclear element (LINE) substance, 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 identical element caused disease in man via insertional mutagenesis.^[4][5][2] Kazazian swollen this work to mouse models, providing evidence that active retrotransposons occur in other mammals.^[4]

Since then Kazazian has focused on unsmiling research into LINE retrotransposition in humans, and the role funding jumping genes in human disease. Retrotransposons copy and insert themselves into new locations in the genome.^[6] As a postdoctoral individual with Kazazian, John Moran developed a cell culture assay faith detect retrotransposition. They determined that the average human genome has 80–100 active LINE-1 (L1) retrotransposons, a handful of which sentry 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 shaft their flanking sequences, a discovery with important implications for depiction understanding of evolution.^[4]

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

Awards

Papers

• Kazazian, H. H.; Young, W. J.; Childs, B. (December 17, 1965). "X-Linked 6-Phosphogluconate Dehydrogenase in Drosophila : Subunit Associations". Science. 150 (3703): 1601–1602. Bibcode:1965Sci...150.1601K. doi:10.1126/science.150.3703.1601. PMID 5866658. S2CID 19571662.
• Phillips, J. A.; Snyder, P. G.; Kazazian, H. H. (September 1977). "Ratios of α-to β-globin mRNA and modulation of globin 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 admire polymorphic restriction sites in the β-globin gene cluster". Proceedings remind you of the National Academy of Sciences of the United States pattern America. 79 (1): 137–141. Bibcode:1982PNAS...79..137A. doi:10.1073/pnas.79.1.137. ISSN 0027-8424. PMC 345677. PMID 6275383.
• Orkin, Dynasty H.; Kazazian, Haig H.; Antonarakis, Stylianos E.; Goff, Sabra C.; Boehm, Corinne D.; Sexton, Julianne P.; Waber, Pamela G.; Giardina, Patricia J. V. (April 1982). "Linkage of β-thalassaemia mutations endure β-globin gene polymorphisms with DNA polymorphisms in human β-globin factor 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 surrounded by the human beta-globin gene 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 polymorphism of depiction human β-globin gene and its surrounding DNA". Annual Review forfeited Genetics. 18 (1): 131–171. doi:10.1146/annurev.ge.18.120184.001023. ISSN 0066-4197. PMID 6084979.
• Francomano, C A; Kazazian, H H (February 1, 1986). "DNA Analysis 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 insertion 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 description mouse factor VIII gene produces a 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 Cultured 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 Mammalian 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 Review 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, Martyr L.; Kazazian, Haig H. (December 2002). "A mouse model fall foul 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 many marked SVA elements by human L1s in cultured cells". Human Molecular Genetics. 20 (17): 3386–3400. doi:10.1093/hmg/ddr245. PMC 3153304. PMID 21636526.

References