In memoriam of Evgeny Iosifovich Schwartz
- 作者: Gorbunova V.N.1
-
隶属关系:
- St. Petersburg State Pediatric Medical University, Ministry of Healthcare of the Russian Federation
- 期: 卷 11, 编号 4 (2020)
- 页面: 99-105
- 栏目: Anniversaries
- URL: https://journals.eco-vector.com/pediatr/article/view/54395
- DOI: https://doi.org/10.17816/PED11499-105
- ID: 54395
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详细
E.I. Schwartz stood at the foundation of Russian molecular genetics: he was the first to apply the novel method of polymerase chain reaction (PCR) in this country. E.I. Schwartz graduated from the LPMI at 1967. His area of research belonged at first to the realm of the metabolic manifestations of hereditary diseases. Since 1985, he began working at the Laboratory of Molecular Genetics, Leningrad Institute of Nuclear Physics (LINP). Shortly thereafter, E.I. Schwartz began to reproduce and implement the PCR, recently proposed by K. Mullis. Coincidentally, the seemingly purely fundamental studies of thermostable polymerase, which turned out to be the key PCR enzyme, had been independently conducted in LINP and contributed to the success of E.I. Schwartz undertaking. He also initiated the development of the first Russian thermocyclers. He implemented PCR in fruitful long-term research projects on the molecular epidemiology of monogenic diseases: phenylketonuria, familial hypercholesterolemia, hereditary disorders of hemostasis, etc. E.I. Schwartz optimized the methods of isolating nucleic acids from dried blood spots and other sources, “suboptimal” for a laboratory specialist, but ideal for screening and forensic practice. Another field of his research was to elucidate the role of polymorphic alleles in multifactorial diseases. E.I. Schwartz enthusiastically propagated the new molecular approaches among clinicians and laboratory geneticists: he established close and fruitful collaborations between specialists of the vastly divergent backgrounds. In 1989 E.I. Schwartz founded the Department of Medical Genetics of LPMI, which was one of the first such departments in U.S.S.R. In 2001, he founded the Department of Molecular Genetic Technologies in I.P. Pavlov`s St. Petersburg State Medical University. In 2003, E.I. Schwartz has passed away, leaving behind him the good memory of numerous students and successors of his work
全文:
This year marks the 80th year since the birth of Professor Evgeny Iosifovich Schwartz and the 17th year since this outstanding scientist has passed away. E.I. Schwartz was born just before the war broke out in Bobruisk City, Belarus. He cherished the memory of his father, a military pilot, who died in battles near Moscow in 1942. As a child, Schwartz’s character was largely under the influence of his stepfather, who was the commander of reconnoiters in the partisan unit during the war period, where Schwartz and his mother were hiding from the Germans, and who worked as a director of a school in Bobruisk after the war.
In 1961, Schwartz entered the Leningrad Pediatric Medical Institute. In his student years, he became interested in biochemistry and genetics and studied enthusiastically these subjects at the Student Research Society under the leadership of Elena Aleksandrovna Savelyeva-Vasilyeva, who he remembered fondly throughout his life. Oleg Aleksandrovich Rosenberg, Viktor Glebovich Vakharlovsky, and Vyacheslav Veniaminovich Krasilnikov, who later became prominent specialists in the field of biochemical and clinical genetics, were also engaged in this Student Research Society at different times. After his graduation from the institute, Schwartz had no doubts in choosing the direction of his scientific and practical activities, and he made various efforts to enter the recently organized academic group of Evgenia Fedorovna Davidenkova, where conducted research on cytogenetics, clinical genetics, and biochemical human genetics. In 1971, Schwartz defended his PhD thesis, “Disorders of carbohydrate metabolism in muscle tissue of patients with Duchenne muscular dystrophy,” [14] and his doctorate thesis, “Metabolic bases of immunological disorders in cells with trisomy on chromosome 21” in 1982 [15]. Based on the results of his study, Schwartz hypothesized that immunological disorders in Down’s syndrome are caused by impaired DNA repair, which, in combination with accelerated tissue catabolism, leads to increased concentration of deoxynucleotides, inhibition of the T-system of immunity, and the development of metabolic immunosuppression.
At that time, many geneticists, including Schwartz, were focused on molecular medicine, and the academic group became insufficient for him. In 1985, he started to work in the laboratory of molecular genetics of the V.P. Konstantinov Leningrad Institute of Nuclear Physics, RAS, which was headed by Vladislav Aleksandrovich Lantsov, a student of Semyon Efimovich Bresler, who was a leading specialist in physical chemistry and biophysics and one of the founders of Russian molecular biology.
Schwartz managed to convince V.A. Lantsov to conduct molecular research not only on microorganisms, which was performed in the laboratory before Schwartz came to work there, but also on models of hereditary human diseases. To implement this idea, a working group was quickly formed by Schwartz, and in 1992, they created a separate laboratory of human molecular genetics and employed well-known researchers such as A.A. Goltsov, S.E. Khalchitsky, and A.I. Kuzmin. In 1985–1986, the group was engaged in the construction of a cDNA library of liver genes based on bacteriophage λgt10 for the analysis of genes of hereditary human diseases, in particular, phenylketonuria [12]. In this work, which was performed jointly with employees of several institutions in Moscow, a first in the country, various methods of genetic engineering were established.
Shortly after the completion of this 2-year laborious work, publications appeared on the invention of the polymerase chain reaction (PCR) method, which greatly facilitated the molecular diagnostics of mutations. Schwartz promptly made a decision to master this new technology as soon as possible [13], which required certain amount of courage. Work on the creation of a gene library has just been successfully completed, and the path to molecular diagnostics of mutations has been opened. However, a new effective diagnostic method emerged, and Schwartz, having overcome his ambitions, fostered all his efforts to its development [6, 7, 11]. Certain prerequisites were already set for this in the laboratory.
Long before the discovery of PCR in the laboratory of molecular diagnostics, studies of DNA replication under extreme conditions, such as elevated temperatures, were already conducted. To solve this problem, the topic executive O.K. Kaboev developed a method for isolation and purification of thermophilic DNA polymerase from the culture of bacteria living in the hot springs of Kuril Islands. This enzyme was necessary for PCR, and its quality was quite satisfactory. In addition, the specificity of PCR is determined by the presence in the reaction mixture of short oligonucleotides complementary to the ends of the synthesized DNA fragment, so-called primers. At that time, their production was also challenging. However, an agreement on their synthesis was achieved with Professor Yu. A. Berlin from the Moscow Institute of Bioorganic Chemistry. No devices were established for automatic PCR (amplifiers or thermal cyclers), and the work was performed manually by rearranging test tube racks in water baths in a certain temperature. Reaction conditions, temperature, and time regimens were worked out experimentally. Schwartz realized the importance of PCR for molecular diagnostics and initiated work on the creation of Russian amplifiers, which were developed on Peltier elements by a group of researchers led by Alexander Tretyakov.
Thus, under the guidance and direct participation of Schwartz, the PCR method was established for the first time in Russia and was used to diagnose mutations in the genes involved in β-thalassemia, phenylketonuria [4, 11], and later cystic fibrosis [16], as well as for genomic fingerprinting, which is now widely used in forensic medicine [26].
The discovery of PCR was a revolutionary event in the field of molecular genetics. Studies of individual genetic characteristics using genomic and cDNA library technologies required a huge amount of work, time, and costs. PCR enabled analysis extremely quickly, determination of the nucleotide sequence of the genome region of interest, ordering of primers, and obtaining information about mutations in an individual just within a few days.
One of the authors helped improve the PCR method, as it was applied to the analysis of blood stains immobilized on various carriers, such as Guthrie test strips, nylon filters, and filter paper, which greatly facilitated and accelerated the rather laborious work of collecting, storing, and transferring of biological material. This was also the undoubted priority of Schwartz’s laboratory [27, 29, 30].
Schwartz was a member of the problem commission on human molecular genetics of the USSR Ministry of Health from 1987 to 1991. For many years and until the end of his life, he was an editorial board member of the international journal Molecular Genetics and Metabolism.
Schwartz was a staunch supporter of the need to introduce theoretical developments in the field of medical genetics into the clinical practice of doctors. In 1989, at his urgent request, a scientific and educational complex was created at the Leningrad Pediatric Institute, which, along with the training Department of Medical Genetics, included his scientific laboratory of human molecular genetics at the Leningrad Institute of Nuclear Physics (LINP). On the basis of this complex, students and teachers of clinical departments of pediatric and other medical institutions could learn practical methods of DNA diagnostics and could conduct scientific research in specific areas of molecular medicine.
The idea of creating such a complex, which was located in a clinical institution, and combining an academic laboratory and a training department was supported by the administration of the Pediatric Institute, primarily by Professor Vyacheslav Petrovich Alferov, its rector, and by Viktor Nikolaevich Fomichev, the head of the department of molecular and radiation biology of LINP, which ensured its further promotion in the Academy of Medical Sciences. It was financially supported by the USSR Ministry of Health.
Schwartz managed to strike a spark out of well-known specialists from various medical institutions of the city, who already had academic degrees and ranks, and to involve them to work at the Department of Medical Genetics of the Pediatric Institute. Although they did not have teaching experience at a medical university, in which the staff of the department was under the leadership of Schwartz, a unique system of genetic education for future doctors was developed.
The results of the scientific activity of the complex were impressive. Two main principles predetermined this success, namely, close interaction with the clinical departments of the Pediatric Academy and some other medical institutions of the city and the involvement of a large number of young specialists, both doctors and laboratory assistants, many of whom graduated from the Department of Biophysics of the Leningrad Polytechnic Institute, which was organized by S.E. Bresler, or the Technological Institute.
The emphasis on scientific research was focused not only on the study of the molecular nature of monogenic diseases, but also on the analysis of genetic risk factors that predispose to the development of the most common socially significant multifactorial pathology. Research in this direction had not yet been conducted in Russia.
A year after its creation, the complex cooperated with the Department of Faculty Therapy of the Pediatric Academy, headed by Yuri Romanovich Kovalev, to investigate the hereditary predisposition to ischemic heart disease and arterial hypertension [9, 20, 22, 25, 31]. Since 1992, the Department of Pediatrics No. 3, headed by Igor Mikhailovich Vorontsov, has also been involved in these studies. A new scientific field was then created, which was associated with the analysis of childhood predisposition to cardiovascular diseases [5, 8]. Together with the Department of Faculty Pediatrics, headed by Albert Vazgenovich Papayan, a series of studies was carried out to investigate the pathogenetic mechanisms of the development of arterial and venous thrombosis in children with normal health status and in children with nephropathies [10, 30].
Contacts of Schwartz’s laboratory with medical institutions were not limited to the Pediatric Academy. Thus, together with the laboratory of biochemical genetics of the Institute of Experimental Medicine (headed by the corresponding member of the Russian Academy of Medical Sciences Vladimir Solomonovich Gaitskhoki), the range of mutations in familial hypercholesterolemia was explored [21, 23, 26]. Since 1997, research in the field of molecular cardiology has been conducted in close cooperation with the Department of Faculty Therapy of the First Leningrad Medical Institute, headed by Vladimir Andreevich Almazov and then Evgeny Vladimirovich Shlyakhto [1, 2]. One of the most interesting areas of scientific research at this time was the study of genetic risk factors for the development of vascular complications in diabetes [28]. The studies on genetic predisposition and hereditary forms of Parkinson’s disease have represented a separate scope [17–19]. At this time, over 20 theses were defended under the guidance of E.I. Schwartz.
Great practical and friendly assistance to the young workers of E.I. Schwartz’s laboratory was provided by the staff of the LINP Laboratory of Molecular Genetics, headed by Professor V.A. Lantsov. This laboratory, like Schwartz’s laboratory, was geographically located in the Consultative and Diagnostic Center of the Pediatric Institute.
An important result of the ongoing research was the creation of unique DNA banks of young and old patients with myocardial infarction and patients with ischemic thrombotic stroke, venous thrombosis, varicose veins, arterial hypertension, type 1 diabetes mellitus, bronchopulmonary pathology, and Parkinson’s disease.
The atmosphere in the laboratory should be separately highlighted. The youth set the tone there. Every day, Schwartz discussed previous events daily with each of the employees, whether they were graduate students, residents, or laboratory assistants, and developed a plan for further actions. He took the failures and blunders of young specialists sincerely and was quite strict with them but democratic and understanding of their personal problems. As a passionate person, Schwartz could not always restrain his emotions. He absolutely did not tolerate betrayal, and sometimes, even with the slightest suspicion, which was often not always well-grounded, he could abruptly switch from love to hate. However, he was also quite demanding of himself. Such an indifferent attitude of the chief to the employees and their research evoked a reciprocal respect, sometimes turning into adoration.
A very important organizing moment in the activities of both the department and the laboratory were weekly scientific seminars held by Schwartz himself. He had comprehensive scientific knowledge, and not a single current publication on human molecular genetics remained unaddressed by him. This was also enhanced by the information support of LINP, which was excellent for that time. In the absence of the Internet, new acquisitions from the Library of the Academy of Sciences was brought to the institute on a weekly basis, and it was possible to order a photocopy of the article from any magazine and receive it promptly. However, most importantly, Schwartz spent every Saturday in the public library and was very happy to meet his employees. He was permitted to take out magazines, brought them to work in large quantities, and photocopy the necessary ones. Reports from employees on the state of affairs in the developed fields were regularly presented at seminars, as well as in reviews on the most pressing issues of modern genetics, and there was a hot dispute on whether the speaker was less informed than the head.
The joint fun feasts should be mentioned, as it also contributed to the friendly atmosphere in the laboratory. They celebrated together official holidays, birthdays, or other pleasant events. Schwartz shone at these celebrations with his wit and great sense of humor.
In 2001, with the support of the rector, academician N.A. Yaitsky and Vice Rector for Science Professor E.E. Zvartau, Schwartz organized the Department of Molecular Genetic Technologies at the I.P. Pavlov First St. Petersburg State Medical University and went there to work with the staff of his laboratory. Along with the continuation of research on molecular cardiology and Parkinson’s disease, research on hereditary forms of thrombophilia and pharmacogenetics became a priority [3, 24]. The Department of Medical Genetics still exists at the Pediatric Academy.
Schwartz’s activities were not limited to the institutions of St. Petersburg. In 2000, he was an employee of Transgenomic Gaithersburg MD (USA). In 2001–2003, he actively contributed to the development of molecular genetic research at the Research Institute of Physical and Chemical Medicine and the Scientific Center for Children’s Health of the Russian Academy of Medical Sciences in Moscow.
The life of E.I. Schwartz ended unexpectedly when he and his wife were stuck in a traffic jam on their way from the summer cottage. He had a heart attack, but there were no drugs to stop it. Being entirely consumed with science and handling carefully the smallest details of his research, he spent all his energy on promoting his labor of love and did not care about himself and his health at all.
Most of the young people schooled by E.I. Schwartz scattered worldwide. Only few chose to stay, namely, S.N. Pchelina, O.V. Sirotkina, S.E. Khalchitsky, and V.I. Larionova. Schwartz’s students successfully continue genetic research in various Russian and international laboratories, but each of them fondly remembers his/her first teacher.
The author expresses gratitude to Sergei Yegorovich Khalchitsky and Yana Efimovna Vilk, the widow of Evgeny Iosifovich Schwartz, for reading the manuscript and providing valuable comments.
作者简介
Victoria Gorbunova
St. Petersburg State Pediatric Medical University, Ministry of Healthcare of the Russian Federation
编辑信件的主要联系方式.
Email: vngor@mail.ru
PhD, Professor, Department of Medical Genetics
俄罗斯联邦, Saint Petersburg参考
- Беркович О.А., Баженова Е.А., Волкова Е.В., и др. А1166С полиморфизм гена рецептора 1 типа ангиотеногена II и дисфункция эндотелия у мужчин, перенесших инфаркт миокарда в молодом возрасте // Российский кардиологический журнал. – 2000. – Т. 5. – № 6. – С. 5–9. [Berkovich OA, Bazhenova EA, Volkova EV, et al. A1166C polymorphism of the gene for angiotensin ii receptor 1st type and endothelial dysfunction in men with a history of myocardial infarction in young age. Russian journal of cardiology. 2000;5(6):5-9. (In Russ.)]
- Беркович О.А., Баженова Е.А., Волкова Е.В., и др. I/D полиморфизм гена ангиотензинпревращающего фермента у мужчин, перенесших инфаркт миокарда // Российский физиологический журнал им. И.М. Сеченова. – 2001. – Т. 87. – № 5. – С. 642–648. [Berkovich OA, Bazhenova EA, Volkova EV, et al. I/D polymorphism in the angiotensin-converting enzyme gene in men with myocardial infarction at young age. Russian journal of physiology. 2001;87(5):642-648. (In Russ.)]
- Вавилова Т.В., Сироткина О.В., Кадинская М.И., и др. Структурные полиморфизмы гена CYP2C9 и их значение в профилактике тромбоэмболических осложнений варфарином у больных с искусственными клапанами сердца // Ученые записки Санкт-Петербургского государственного медицинского университета им. акад. И.П. Павлова. – 2003. – Т. 10. – № 4. – С. 40–46. [Vavilova TV, Sirotkina OV, Kadinskaya MI, et al. Strucural polymorphisms in CYP2C9 gene and their significance in the prophylaxis of thromboembolic complcations in patients with artificial heart valves. The Scientific notes of the I.P. Pavlov St. Petersburg State medical university. 2003;10(4):40-46. (In Russ.)]
- Гольцов А.А., Сурин В.Л., Лукьяненко А.В., и др. Характер двух мутационных повреждений β-глобинового гена при β0-талассемии в Азербайджане // Биоорганическая химия. – 1989. – Т. 15. – № 7. – С. 1001–1002. [Gol’tsov AA, Surin VL, Luk’yanenko AV, et al. The nature of the two mutational lesions of the β-globin gene in β0-thalassemia in Azerbaijan. Russian journal of bioorganic chemistry. 1989;15(7):1001-1002. (In Russ.)]
- Горбунова В.Н. Молекулярная генетика — путь к индивидуальной персонализированной медицине // Педиатр. – 2013. – Т. 4. – № 1. – C. 115–121. [Gorbunova VN. Molecular genetics – a way to the individual personalized medicine. Pediatr. 2013;4(1):115-121. (In Russ.)]. https://doi.org/10.17816/PED41115-121.
- Горбунова В.Н., Баранов В.С. Введение в молекулярную диагностику и генотерапию наследственных заболеваний: учебное пособие для студентов медицинских вузов. – СПб., 1997. – 287 c. [Gorbunova VN, Baranov VS. Vvedenie v molekulyarnuyu diagnostiku i genoterapiyu nasledstvennykh zabolevaniy: uchebnoe posobie dlya studentov meditsinskikh vuzov. Saint Petersburg; 1997. 287 p. (In Russ.)]
- Данилова Л.А., Башарина О.Б., Красникова Е.Н., др. Справочник по лабораторным методам исследования / Под ред. Л.А. Даниловой. – М.: Питер, 2003. – 733 с. [Danilova LA, Basharina OB, Krasnikova EN, et al. Spravochnik po laboratornym metodam issledovaniya. Ed. by L.A. Danilovа. Moscow: Piter; 2003. 733 p. (In Russ.)]
- Демидова Д.В., Ларионова В.И., Волкова М.В., и др. Анализ влияния структуры генов липопротеиновой липазы, аполипопротеинов СIII и аполипопротеина Е на развитие комбинированной гиперлипидемии // Кардиология. – 2001. – T. 41. – № 8. – С. 17–22. [Demidova DV, Larionova VI, Volkova MV, et al. The analysis of the lipoprotein lipase, apolipoprotein СIII and apolipoprotein E gene structure impact on the development of the combined hyperlipidemia. Kardiologiya. 2001;41(8):17-22. (In Russ.)]
- Нефедова Ю.Б., Шварц Е.И. Молекулярно-генетические механизмы развития артериальной гипертензии // Артериальная гипертензия. – 1998. – T. 4. – № 3. – C. 63–71. [Nefedova YuB, Shvarts EI. Molekulyarno-geneticheskie mekhanizmy razvitiya arterial’noi gipertenzii. Arterial hypertension. 1998;4(3):63–71. (In Russ.)]
- Папаян Л.П., Кобелянская В.А., Шейдина А.М., и др. Изменения в системе гемостаза у больных с наследственной тромбофилией, обусловленной мутацией фактора V свертывания крови (фактор V Лейден) // Терапевтический архив. – 2001. – Т. 73. – № 7. – С. 47–51. [Papayan LP, Kobelyanskaya VA, Sheydina AM, et al. The changes of the hemostatic system in patients with hereditary thrombophilia, caused by the mutation of factor V of the blood coagulation (factor V Leiden). Therapeutic archive. 2001;73(7):47-51. (In Russ.)]
- Скрябин Б.В., Ковальчук Л.А., Хальчицкий С.Е., и др. Определение природы мутационного повреждения в 12-м экзоне фенилаланингидроксилазного гена у больных фенилкетонурией // Биоорганическая химия. – 1989. – Т. 15. – № 12. – С. 1690–1692. [Skryabin BV, Koval’chuk LA, Khal’chitskiy SE, et al. The evaluation of the nature of the mutational lesion in the exon 12 of the phenylalanine hydroxylase gene in patients with phenylketonuria. Russian journal of bioorganic chemistry. 1989;15(12):1690-1692. (In Russ.)]
- Хальчицкий С.Е., Ищенко И.Д., Гольцов А.А., и др. Конструирование и характеристика к ДНК-овой клонотеки эмбриональной печени человека на основе бактериофага &л dt10. – Л.: ЛИЯФ, 1987. – 19 с. [Hal’chitskiy SE, Ishchenko ID, Gol’tsov AA, et al. Konstruirovanie i kharakteristika k DNK-ovoy klonoteki embrional’noy pecheni cheloveka na osnove bakteriofaga &л gt10. Leningrad: LIYAF; 1987. 19 p. (In Russ.)]
- Хальчицкий С.Е. Евгений Иосифович Шварц и первая ПЦР в СССР // Молекулярные основы клинической медицины — возможное и реальное: сборник материалов 3-го Российского конгресса с международным участием, 26–29 марта 2015 г. – СПб., 2015. – С. 25–29. [Khal’chitskii SE. Evgenii Iosifovich Shvarts i pervaya PTSR v SSSR. (Conference proceedings) Molekulyarnye osnovy klinicheskoi meditsiny — vozmozhnoe i real’noe: sbornik materialov 3-go Rossiiskogo kongressa s mezhdunarodnym uchastiem, 2015 March 26–29. Saint Petersburg; 2015. C. 25-29. (In Russ.)]
- Шварц Е.И. Нарушения углеводного метаболизма в мышечной ткани больных миодистрофией Дюшенна. – Л., 1971. – 20 c. [Shvarts EI. Narusheniya uglevodnogo metabolizma v myshechnoy tkani bol’nykh miodistrofiey Dyushenna. Leningrad; 1971. 20 p. (In Russ.)]
- Шварц Е.И. Метаболические основы иммунологических нарушений в клетках с трисомией по 21 хромосоме. – Л., 1982. – 35 c. [Shvarts EI. Metabolicheskie osnovy immunologicheskikh narusheniy v kletkakh s trisomiey po 21 khromosome. Leningrad; 1982. 35 p. (In Russ.)]
- Шварц Е.И., Иващенко Т.Э., Гольцов А. А., и др. Использование метода цепной реакции синтеза ДНК для анализа частоты рестрикционного полиморфизма ДНК-локуса CS-7 в популяции и в семьях больных муковисцидозом // Доклады Академии Наук СССР. – 1989. – Т. 307. – № 2. – С. 467–469. [Shvarts EI, Ivashchenko TE, Gol’tsov AA, et al. DNA polymerase chain reaction in analysis of restriction polymorphism frequency of the DNA locus CS-7 in the population and in families of patients with mucoviscidosis. Doklady Akademii Nauk SSSR. 1989;307(2): 467-469. (In Russ.)]
- Якимовский А.Ф., Пушнова Е.А., Ахмедова С.Н., Автономов В.В. Молекулярно-генетические и токсико-экологические основы этиологии и патогенеза болезни Паркинсона (паркинсонизма) // Журнал неврологии и психиатрии им. C.C. Корсакова. – 1997. – T. 97. – № 4. – C. 69–73. [Yakimovskiy AF, Pushnova EA, Akhmedova SN, Avtonomov VV. Molecular-genetic and toxico-ecological basis of the etiology and pathogenesis of the Parkinson disease (parkinsonism). S.S. Korsakov journal of neurology and psychiatry. 1997;97(4):69-73. (In Russ.)]
- Akhmedova S, Anisimov S, Yakimovsky A, Schwartz E. Gln-Arg 191 polymorphism of paraoxonase and Parkinson’s disease. Hum Hered. 1999;49(3):178-180. https://doi.org/10.1159/000022868.
- Akhmedova SN, Yakimovsky AK, Schwartz E. Paraoxonase 1 Met-Leu 54 polymorphism is associated with Parkinson’s disease. J Neurol Sci. 2001;184(2):179-182. https://doi.org/10.1016/s0022-510x(01)00439-7.
- Baranovskaya S, Kudinov S, Fomicheva E, et al. Age as a risk factor for myocardial infarction in Leiden mutation carriers. Mol Genet Metab. 1998;64(2):155-157. https://doi.org/10.1006/mgme.1998.2697.
- Chakir K, Skobeleva NA, Schevtsov SP, et al. Two novel slavic point mutations in the low density lipoprotein receptor gene in patients with familial hypercholesterolemia in St. Petersburg, Russia. Mol Genet Metab. 1998;63(1):31-34. https://doi.org/10.1006/mgme.1997.2614.
- Fomicheva E, Gukova S, Larionova-Vasina V, et al. Gene-gene interaction in the RAS system in the predisposition to myocardial infarction in elder population of St. Petersburg (Russia). Mol Genet Metab. 2000;69(1):76-80. https://doi.org/10.1006/mgme.1999.2924.
- Mandelshtam M, Chakir K, Shevtsov S, et al. Prevalence of Lithuanian mutation among St. Petersburg Jews with familial hypercholesterolemia. Hum Mut. 1998;12(4):255-258. https://doi.org/10.1002/(SICI)1098-1004(1998)12:4<255:: AID-HUMU6>3.0.CO;2-E.
- Pchelina SN, Sirotkina OV, Taraskina AE, et al. The frequency of cytochrome P450 2C9 genetic variants in Russian population and their associations with individual sensitivity to warfarin therapy. Thromb Res. 2005;115(3):199-203. https://doi.org/10.1016/j.thromres.2004.08.020.
- Popov V, Fomicheva E, Kovalev J, Schwartz E. Absence of association between the angiotensin-converting enzyme gene polymorphism and borderline hypertension in men of St. Petersburg, Russia. J Hum Hypertens. 1996;10(8):557-559.
- Pushnova EA, Ahmedova SN, Shevtsov SP, Schwartz EI. A rapid and simple DNA fingerprinting method by means of RFLP and SSCP analysis of the hypervariable noncoding region of human mitochondrial DNA. Human Mutation. 1994;3:292-296. https://doi.org/10.1002/humu.1380030318.
- Schwartz EI, Khalchitsky SE, Eisensmith RC, Woo SL. Polymerase chain reaction amplification from dried blood spots on Guthrie cards. Lancet. 1990;336(8715): 639-640. https://doi.org/10.1016/0140-6736(90) 93446-v.
- Shcherbak N, Shutskaya Z, Sheidina A, et al. Methelenetetrahydrofolate reductase gene polymorphism as a risk factor for diabetic nephropathy in IDDM patients. Mol Genet Metab. 1999;68(3):375-378. https://doi.org/10.1006/mgme.1999.2909.
- Skryabin BV, Khalchitsky SE, Kuzjmin AI, et al. A crude lysate of cells immobilized on solid support can serve as a matrix for enzymatic DNA amplification. Nucleic Acids Research. 1990;18(14):4289. https://doi.org/10.1093/nar/18.14.4289.
- Sverdlova AM, Bubnova NA, Baranovskaya SS, et al. Prevalence of the Methylenetetrahydrofolate Reductase (MTHFR) C677T Mutation in patients with varicose veins of lower limbs. Mol Genet Metab. 1998;64(1): 35-36. https://doi.org/10.1006/mgme.1997.2638.
- Volkova MV, Vasina (Larionova) VI, Obraztsova GI, Schwartz EI. Identification of the C—>T polymorphism in the +93 position of the apo(a) gene by mismatch PCR-mediated site-directed mutagenesis and restriction enzyme digestion. Biochem Mol Med. 1996;59(1):91-92. https://doi.org/10.1006/bmme. 1996.0071.
补充文件
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