IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860

Aim. The goal of our study was to develop an accurate detection of the SNP rs12979860 by RFLP-based method and to evaluate the polymorphic genotype distribution forthis SNP among individuals with unknown HCV status from Ukraine. Methods.The SNP rs12979860 was tested by PCR RFLP-based method in 99...

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Datum:2011
Hauptverfasser: Pampukha, V.M., Kravchenko, S.A., Moroz, L.V., Livshits, L.A.
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Veröffentlicht: Інститут молекулярної біології і генетики НАН України 2011
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Zitieren:IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860 / V.M. Pampukha, S.A. Kravchenko, L.V. Moroz, L.A. Livshits // Вiopolymers and Cell. — 2011. — Т. 27, № 3. — С. 231-234. — Бібліогр.: 15 назв. — англ.

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spelling irk-123456789-1564042019-06-19T01:25:27Z IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860 Pampukha, V.M. Kravchenko, S.A. Moroz, L.V. Livshits, L.A. Short Communications Aim. The goal of our study was to develop an accurate detection of the SNP rs12979860 by RFLP-based method and to evaluate the polymorphic genotype distribution forthis SNP among individuals with unknown HCV status from Ukraine. Methods.The SNP rs12979860 was tested by PCR RFLP-based method in 99 individuals from Ukraine. Results. The method of accurate detection of the SNP rs12979860 was developed. The genotypes distributions were: CC – 56 %, CT – 34 %, TT – 10 %. Conclusions. Due to the high incidence of CC genotype, found in ourstudy, the SNP rs12979860 analysis may be useful for Ukrainian patientsto predict responsesto the treatment considering the HCV genotype and viral load. Keywords: IFN-l-3 (IL28B) gene, SNP rs12979860, PCR-RFLP method, hepatitis C. Мета. Метою даної роботи була розробка простого методу детекції поліморфізму rs12979860 на основі ПДРФ-аналізу та проведення генотипування за даним поліморфізмом серед індивідів з невизначеним статусом хронічного гепатиту С в популяції України. Методи. SNP rs12979860 проаналізовано методом ПЛР/ ПДРФ серед 99 індивідів з України. Результати. Розроблено точний метод детекції rs12979860 та виявлено такий розподіл генотипів: CC – 56 %, CT – 34 %, TT – 10 %. Висновки. Зважаючи на визначену високу частоту генотипу СС у нашому дослідженні, аналіз поліморфізму rs12979860 можна застосовувати в Україні для прогнозу відповіді пацієнта на лікування з урахуванням генотипу вірусу С і вірусного навантаження. Ключові слова: ген IFN-l-3 (IL28B4), SNP rs12979860, метод ПЛР/ПДРФ, гепатит C. Цель. Цель данной работы состояла в разработке простого метода определения полиморфизма rs12979860 на основе ПДРФанализа и проведение генотипирования по данному полиморфизму среди индивидов с неустановленным статусом хронического гепатита С из Украины. Методы. SNPrs12979860 проанализирован методом ПЦР/ПДРФ среди 99 индивидов из Украины. Результаты. Разработан точный метод детекции rs12979860 и выявлено следующее распределение генотипов в популяции Украины: CC – 56 %, CT – 34 %, TT – 10 %. Выводы. Принимая во внима - ние высокую частоту генотипа СС, определенную в нашем исследовании, можно сделать вывод о том, что анализ полиморфизма rs12979860 целесообразно применять в Украине для прогноза ответа пациента на лечение с учетом генотипа вируса С и вирусной нагрузки. Ключевые слова: ген IFN-l-3 (IL28B4), SNP rs12979860, метод ПЦР/ПДРФ, гепатит C. 2011 Article IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860 / V.M. Pampukha, S.A. Kravchenko, L.V. Moroz, L.A. Livshits // Вiopolymers and Cell. — 2011. — Т. 27, № 3. — С. 231-234. — Бібліогр.: 15 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.0000BE http://dspace.nbuv.gov.ua/handle/123456789/156404 577.21 en Вiopolymers and Cell Інститут молекулярної біології і генетики НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Short Communications
Short Communications
spellingShingle Short Communications
Short Communications
Pampukha, V.M.
Kravchenko, S.A.
Moroz, L.V.
Livshits, L.A.
IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860
Вiopolymers and Cell
description Aim. The goal of our study was to develop an accurate detection of the SNP rs12979860 by RFLP-based method and to evaluate the polymorphic genotype distribution forthis SNP among individuals with unknown HCV status from Ukraine. Methods.The SNP rs12979860 was tested by PCR RFLP-based method in 99 individuals from Ukraine. Results. The method of accurate detection of the SNP rs12979860 was developed. The genotypes distributions were: CC – 56 %, CT – 34 %, TT – 10 %. Conclusions. Due to the high incidence of CC genotype, found in ourstudy, the SNP rs12979860 analysis may be useful for Ukrainian patientsto predict responsesto the treatment considering the HCV genotype and viral load. Keywords: IFN-l-3 (IL28B) gene, SNP rs12979860, PCR-RFLP method, hepatitis C.
format Article
author Pampukha, V.M.
Kravchenko, S.A.
Moroz, L.V.
Livshits, L.A.
author_facet Pampukha, V.M.
Kravchenko, S.A.
Moroz, L.V.
Livshits, L.A.
author_sort Pampukha, V.M.
title IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860
title_short IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860
title_full IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860
title_fullStr IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860
title_full_unstemmed IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860
title_sort ifn-l-3 (il28b) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860
publisher Інститут молекулярної біології і генетики НАН України
publishDate 2011
topic_facet Short Communications
url http://dspace.nbuv.gov.ua/handle/123456789/156404
citation_txt IFN-l-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860 / V.M. Pampukha, S.A. Kravchenko, L.V. Moroz, L.A. Livshits // Вiopolymers and Cell. — 2011. — Т. 27, № 3. — С. 231-234. — Бібліогр.: 15 назв. — англ.
series Вiopolymers and Cell
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fulltext SHORT COMMUNICATIONS IFN-λ-3 (IL28B) genotyping by restriction fragment length polymorphism method: detection polymorphism of rs12979860 V. M. Pampukha, S. A. Kravchenko, L. V. Moroz1, L. A. Livshits Institute of Molecular Biology and Genetics NAS of Ukraine 150, Akademika Zabolotnoho St., Kyiv, Ukraine, 03680 1National Pirogov Memorial Medical University NAMS of Ukraine 56, Pirogova St., Vinnytsya, Ukraine, 21018 livshits@imbg.org.ua Aim. The goal of our study was to develop an accurate detection of the SNP rs12979860 by RFLP-based method and to evaluate the polymorphic genotype distribution for this SNP among individuals with unknown HCV status from Ukraine. Methods.The SNP rs12979860 was tested by PCR RFLP-based method in 99 individuals from Ukraine. Results. The method of accurate detection of the SNP rs12979860 was developed. The genotypes distributions were: CC – 56 %, CT – 34 %, TT – 10 %. Conclusions. Due to the high incidence of CC genotype, found in our study, the SNP rs12979860 analysis may be useful for Ukrainian patients to predict responses to the treatment considering the HCV genotype and viral load. Keywords: IFN-λ-3 (IL28B) gene, SNP rs12979860, PCR-RFLP method, hepatitis C. Introduction. Hepatitis C virus (HCV) infects about 3 % of the world population [1]. Only 20–30 % of HCV-infected individuals recover spontaneously, with remaining 70–80 % developing chronic infection [2]. It was shown that regardless decreasing the incidence of acute hepatitis C, the number of people chronically infected with HCV increases in Ukraine [3]. Chronic HCV infection can lead to the development of cirrhosis and hepatocellular carcinoma [4]. The current standard of care for chronic HCV infection is 24 or 48 weeks of therapy with pegylated interferon-alfa (PEG-IFN) and ribavirin (RBV). A response to the therapy is variable: host and viral characteristics determine whether pa- tients develop a sustained virological response (SVR). The patients infected with HCV genotype 1, who were treated for 48 weeks with PEG-IFN and RBV, have a 50 % possibility of developing SVR. Patients with HCV genotype 2 or 3 have SVR rate 80 % after 24 weeks of the PEG-IFN and RBV therapy [5]. Other factors predictive of response are hepatitis C viral load, patient age, sex, weight, and liver fibrosis stage. Pa- tient’s genetic ancestry is also an important factor in the treatment outcome. The patients of African ancestry with chronic HCV have an almost 50 % reduction in SVR rates at the PEG-IFN and RBV therapy compared with the patients of European ancestry [6]. Recently, four research groups have independently identified single nucleotide polymorphisms (SNPs) linked to the inreferon lambda gene (IFN-λ-3, also known as IL28B) that are associated with response to the PEG-IFN and RBV treatment of HCV-infected individuals of European, Asian and African ancestry [7–10]. Ge et al. identified a SNP 3 kb upstream of the IFN-λ-3 (IL28B) gene, rs12979860, that was strongly associated with SVR. It was shown that CC genotype of rs12979860 was associated with an approximately 231 ISSN 0233–7657. Biopolymers and Cell. 2011. Vol. 27. N 3. P. 231–234  Institute of Molecular Biology and Genetics, NAS of Ukraine, 2011 2-fold greater rate of SVR compared with the TT ge- notype, both among patients of European ancestry and African Americans. Ge et al. sequenced the IFN-λ-3 (IL28) gene in 96 individuals and found two variants in linkage disequilibrium with rs12979860: a G > C tran- sition 27 upstream of the translation initiation codon (rs28416813), and a non-synonymous coding SNP (213A > G, K70R, rs8103142). However, the tests for independence were not possible owing to the high degree of correlation among three SNPs, and it could not be determined which, if any, of the SNPs is uni- quely responsible for the association with SVR [7]. Thomas et al. genotyped the rs12979860 SNP in more than 1000 people with spontaneous clearance of HCV or viral persistence and found that CC genotype was strongly associated with HCV clearance [11]. Because the CC genotype was substantially more frequent in European than African populations, Ge et al. (2009) estimated that rs12979860 could explain ap- proximately half of the difference in SVR between African Americans and the patients of European an- cestry [7]. The goal of our study was to develop simple Res- triction Fragment Length Polymorphism (RFLP)- based method for the detection of polymorphism rs12979860 and to evaluate the polymorphic genotype distribution in population of Ukraine. Materials and methods. Genomic DNA was ex- tracted from the peripheral leukocytes by standard methods in 99 individuals with unknown HVC status from different regions of Ukraine after informed con- sent [12]. Published sequence information of the rs12979860 was used to design a pair of primers spanning this SNP [http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.c gi?rs=12979860]. The polymerase chain reaction (PCR) was carried out under standard conditions. After an initial denaturation step at 94 oC for 4 min, the samples were processed through 5 cycles of amp- lification consisting of: 94 oC temperature for 1 min, primer annealing of 62 oC for 1 min, and extension at 72 oC for 1 min, 10 cycles of amplification consisting of: 94 oC for 1 min, primer annealing of 58 oC for 1 min, and extension at 72 oC for 1 min, 25 cycles of amp- lification consisting of: 94 oC for 1 min, primer an- nealing of 55 oC for 1 min, and extension at 72 oC for 1 min. The final extension step was prolonged to 7 min at 72 oC. The C to T transition (rs12979860) creates the site for Hpy8I restriction enzyme. Amplified DNA (10 µl) was digested in a 20 µl reaction mixture, using the buf- fers and temperatures recommended by the manufac- turers («Fermentas», Lithuania). The amount of rest- riction enzyme required for digestion was 5 U, samples were incubated during overnight. Digested products were fractionated in 2 % agarose gel and visualized by the ethidium bromide staining and transillumination with ultraviolet light. The size marker was GeneRuler 50 bp DNA Ladder («Fermentas»). Statistic analysis was performed using χ2 [13]. Results and discussion. In 2003 Sheppard et al. by genomic sequence analysis identified the IFN-λ-1, IFN-λ-2, IFN-λ-3 genes and described human genes in the type-III interferon family having high conserved sequences (including exons, introns and flanking DNA) and deduced that 200-amino acid IFN-λ-3 protein was 96 % identical to IFN-λ-2 and 81 % identical to IFN-λ-1 [14, 15]. The SNP rs12979860 analysis was complicated due to the existence of site for the restriction enzyme Hpy8I in highly homologous sequence of IFN-λ-2 gene. To avoid the analysis mis- carriage the primers design based on minor sequence mismatch between IFN-λ-2 and IFN-λ-3 genes was performed. The results of SNP rs12979860 genotyping are shown in Figure. The product length after ampli- fication is 430 bp. Hpy8I digestion of the amplification fragment produces a constant 110 bp fragment. The C to T transition was detected due to the exsistence of an additional restriction site for Hpy8I: the T allele is de- fined by the presence of 290 bp band, whereas the allele C is defined by the presence of 320 bp band. The genotypes and allelic distributions among 99 healthy controls were: CC – 56 %, CT – 34 %, TT – 10 %; C – 73 %, T – 27 %. The genotype distribution was in Hardy-Weinberg equilibrium. Thomas et al. reported the allelic frequencies of rs12979860 in dif- ferent ethnic groups. By genotyping more than 2000 healthy individuals from different countries they observed that the protective allele C was most highly prevalent in Asian populations, of intermediate fre- quency in Caucasian individuals, and presented at low 232 PAMPUKHA V. M. ET AL. frequency in African populations [11]. The allelic frequencies for Ukrainian population analyzed do not statistically differ from frequencies of other European populations reported by Thomas et al. and statistically differ (P < 0.05) from Asian and African populations. Conclusions. We have described here a new, rapid, and relatively inexpensive method for the IFN-λ-3 (IL28B) genotyping, using PCR-RFLP approach. Due to the high incidence of CC genotype, revealed in our study and taking into consideration the numerous data, showing that this genotype was associated with high rate of SVR, the rs12979860 analysis may be useful in Ukraine to predict patients’ responses to the treatment considering HCV genotype and viral load. В. М. Пам пу ха, С. А. Крав чен ко, Л. В. Мо роз, Л. А. Лівшиць Ге но ти пу ван ня IFN-λ-3 (IL28B) ме то дом поліморфізму дов жи ни рес трикційних фраг ментів: виз на чен ня поліморфізму rs12979860 Ре зю ме Мета. Ме тою да ної ро бо ти була роз роб ка про сто го ме то ду де - текції поліморфізму rs12979860 на основі ПДРФ-аналізу та про - ве ден ня ге но ти пу ван ня за да ним поліморфізмом се ред індивідів з не виз на че ним ста ту сом хронічно го ге па ти ту С в по пу ляції Укра- їни. Ме то ди. SNP rs12979860 про а налізо ва но ме то дом ПЛР/ ПДРФ се ред 99 індивідів з Украї ни. Ре зуль та ти. Роз роб ле но точ ний ме тод де текції rs12979860 та ви яв ле но та кий роз поділ ге но типів: CC – 56 %, CT – 34 %, TT – 10 %. Вис нов ки. Зва жа ю чи на виз на че ну ви со ку час то ту ге но ти пу СС у на шо му дослідженні, аналіз поліморфізму rs12979860 мож на за сто со ву ва ти в Україні для про гно зу відповіді пацієнта на ліку ван ня з ура ху ван ням ге но - ти пу вірусу С і вірус но го на ван та жен ня. Клю чові сло ва: ген IFN-λ-3 (IL28B4), SNP rs12979860, ме тод ПЛР/ПДРФ, ге па тит C. В. Н. Пам пу ха, С. А. Крав чен ко, Л. В. Мо роз, Л. А. Лив шиц Ге но ти пи ро ва ние IFN-λ-3 (IL28B) ме то дом по ли мор физ ма дли ны рес трик ци он ных фраг мен тов: опре де ле ние по ли мор физ ма rs12979860 Ре зю ме Цель. Цель дан ной ра бо ты со сто я ла в раз ра бот ке про сто го ме - то да опре де ле ния по ли мор физ ма rs12979860 на осно ве ПДРФ- ана ли за и про ве де ние ге но ти пи ро ва ния по дан но му по ли мор физ - му сре ди ин ди ви дов с не уста нов лен ным ста ту сом хро ни чес ко го ге па ти та С из Укра и ны. Ме то ды. SNPrs12979860 про а на ли зи ро - ван ме то дом ПЦР/ПДРФ сре ди 99 ин ди ви дов из Укра и ны. Ре зуль - та ты. Раз ра бо тан точ ный ме тод де тек ции rs12979860 и вы- яв ле но сле ду ю щее рас пре де ле ние ге но ти пов в по пу ля ции Укра и - ны: CC – 56 %, CT – 34 %, TT – 10 %. Вы во ды. При ни мая во вни ма - ние вы со кую час то ту ге но ти па СС, опре де лен ную в на шем ис- сле до ва нии, мож но сде лать вы вод о том, что ана лиз по ли мор - физ ма rs12979860 це ле со об раз но при ме нять в Укра и не для про - гно за от ве та па ци ен та на ле че ние с уче том ге но ти па ви ру са С и ви рус ной на груз ки. Клю че вые сло ва: ген IFN-λ-3 (IL28B4), SNP rs12979860, ме тод ПЦР/ПДРФ, ге па тит C. REFERENCES 1. World Health Organization: Global surveillance and control of hepatitis C. Report of a WHO consultation organized in col- laboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium // J. Viral. Hepat.–1999.–6, N 1.–P. 35–47. 2. Micallef J. M., Kaldor J. M., Dore G. J. Spontaneous viral clea- rance following acute hepatitis C infection: a systematic review of longitudinal studies // J. Viral. Hepat.–2006.–13, N 1.– P. 34–41. 3. Gural A. L., Marievskiy V. F., Sergeyeva T. A., Shaginyan V. R., Ruban O. M. 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I., Alexander G., Goedert J. J., Kirk G. D., Donfield S. M., Rosen H. R., Tobler L. H., Busch M. P., McHutchison J. G., Goldstein D. B., Carrington M. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus // Nature.–2009.–461, N 7265.–P. 798–801. 12. Sambrook J., Frtsch E. F., Maniatis T. Molecular cloning: a labora- tory manual.–New York: Cold Spring Harbor Lab. press, 1989.– 253 p. 13. Weir B. S. Genetic data analysis. Methods for discrete popula- tion genetic data.–Sunderland: Sinauer Associates, Inc. Publ., 1990.–377 p. 14. Sheppard P., Kindsvogel W., Xu W., Henderson K., Schlutsme- yer S., Whitmore T. E., Kuestner R., Garrigues U., Birks C., Ro- raback J., Ostrander C., Dong D. IL-28, IL-29 and their class II cytokine receptor IL-28R // Nat. Immunol.–2003.–4, N 1.– P. 63–68. 15. Fox B. A., Sheppard P. O., O’Hara P. J. The role of genomic da- ta in the discovery, annotation and evolutionary interpretation of the interferon-lambda family // PLoS One.–2009.–4, N 3.– e4933. UDC 577.21 Received 10.03.11 234 PAMPUKHA V. M. ET AL.