Идентификация генов хромосомы 19 человека вблизи LTR эндогенного ретровируса HFRV-K тема диссертации и автореферата по ВАК РФ 03.00.03, кандидат биологических наук Хиль, Павел Павлович

• Хиль, Павел Павлович
• кандидат биологических наук
• 1999

Оглавление диссертации кандидат биологических наук Хиль, Павел Павлович

ВВЕДЕНИЕ

ЭНДОГЕННЫЕ РЕТРОВИРУСЫ ЧЕЛОВЕКА: НХ РОЛЬ В

ФУНКЦИОНИРОВАНИИ ГЕНОМА (ОБЗОР ЛИТЕРАТУРЫ)

Введение

Эндогенные ретровирусы и родственные им последовательности в геноме

человека

Роль эндогенных ретровирусов в функционировании генома человека

Заключение

РЕЗУЛЬТАТЫ ЭКСПЕРИМЕНТОВ И ИХ ОБСУЖДЕНИЕ

Введение

Стратегия, использованная для идентификации генов в локусах хромосомы

человека содержащих LTR эндогенногоретровируса семейства HERV-K

кДНК селекция на космиды, содержащие LTR HERV-K

Анализ обогащенных кДНК библиотек

Выделение индивидуальных фрагментов кДНК, специфичных к определенным

локусам хромосомы 19 человека и их последующее секвенирование

Точное картирование на хромосоме 19 человека идентифицированных генов и

определение их взаиморасположения с LTR HERV-K

Определение тканеспецифичности экспрессии идентифицированных

потенциальных генов

Высокоразрешающее взаимное картирование кодирующих областей гена ZNF91 и

LTRHERV-K

Идентификация и характеристика вариантов транскриптов гена р31

регуляторной субъединицы 26S протеасомы

Характеристика потенциального гена со специфической экспрессией в тканях

мозга человека

Сравнительный структурный анализ индивидуальных LTR

ЭКСПЕРИМЕНТАЛЬНАЯ ЧАСТЬ

Оборудование и расходные материалы

Реактивы и ферменты

Штаммы, культуры, плазмиды

Космидные библиотеки

PCR-амплификация

кДНК селекция

Клонирование продуктов кДНК селекции

In Vitro клонирование

Southern- и Northern-блот гибридизация

Выделение РНК

RT-PCR

RACE

ВЫВОДЫ

БЛАГОДАРНОСТИ

СПИСОК ЛИТЕРАТУРЫ

Введение диссертации (часть автореферата) на тему «Идентификация генов хромосомы 19 человека вблизи LTR эндогенного ретровируса HFRV-K»

ВВЕДЕНИЕ

Эндогенные ретровирусы человека (Human Endogenous Retroviruses, HERV) представляют собой стабильно наследуемые геномные последовательности, сходные по структуре с геномами ретровирусов. Полагают, что они являются потомками экзогенных ретровирусов, внедрившихся в геном предшественников человека. В геноме человека обнаружено более десяти семейств таких последовательностей, как сохранивших в разной степени измененные остатки генов ретро-вирусов, так и существующих в виде отдельных длинных концевых повторов (Long Terminal Repeals, LTR). Они могут также рассматриваться как мобильные генетические элементы, способные вызывать многочисленные мутации в геномах хозяев. По сделанным оценкам, по меньшей мере 1 % генома человека состоит из последовательностей HERV. Описано несколько типов HERV отличающихся друг от друга, в частности типом тРНК осуществляющей инициацию обратной транскрипции. В соответствии с этим признаком HERV классифицируют как HERV-E (инициатор — тРНК глутаминовой кислоты), HERV-H (гистидиновая тРНК), HERV-К (лизиновая тРНК) и т.д.

Биологическая роль и патогенный потенциал HERV пока неясны. Однако существует ряд данных об участии HERV в регуляции экспрессии генов, в опухо-леобразовании, предотвращении заражения похожими экзогенными ретровиру-сами, иммуносупрессии, а также в качестве патогенных агентов при некоторых аутоиммунных заболеваниях. Предполагается их связь с такими заболеваниями, как диабет и рассеянный склероз.

LTR включают в себя множество элементов, регулирующих транскрипцию — промоторов, энхансеров, элементов гормональной регуляции, сигналов поли-аденилирования — вследствие чего могут вызывать существенные изменения в картине экспрессии близлежащих генов человека. Обнаружение LTR-pery-лируемых генов является, таким образом, актуальным направлением в изучении механизмов регуляции экспрессии генов, в исследовании полиморфизма и эволюции, как отдельных генов человека, так и генома в целом. Задачей данной работы был структурный анализ последовательностей LTR HERV-К и идентификация кандидатных генов вблизи отдельных LTR на хромосоме 19 человека. В качестве объекта исследования был выбран HERV-K, поскольку именно это семейство эндогенных ретровирусов человека в наибольшей степени сохранило функциональный потенциал.

Заключение диссертации по теме «Молекулярная биология», Хиль, Павел Павлович

выводы

1. С помощью разработанной высокоэффективной методики произведена селекция кДНК для 32 космид, содержащих вставки из различных областей хромосомы 19 человека.

2. Идентифицировано 4 новых гена человека, находящихся на хромосоме 19.

3. Произведено высокоразрешающее физическое картирование идентифицированных фрагментов кДНК на хромосоме 19 человека. Определено взаиморасположение кодирующих областей и ЬТЛ эндогенного ретровируса семейства НЕКУ-К.

4. Исследована тканеспецифичность экспрессии идентифицированных генов.

5. Разработана систематика и рассчитано время возникновения в геноме отдельных групп 1ЛИ.

Список литературы диссертационного исследования кандидат биологических наук Хиль, Павел Павлович, 1999 год

СПИСОК ЛИТЕРАТУРЫ

1. Baltimore, D. (1985) Retroviruses and retrotransposons: the role of reverse transcription in shaping the eukaryotic genome. Cell, v. 40, 481-482.

2. Wilkinson, D.A., Mager, D.L. and Leong, J.A.C. (1994) Endogenous human retroviruses, p. 465-535, in J. A. Levy (ed.), The Retroviridae, vol.3 Plenum Press, New York.

3. Larsson, E., Kato, N. and Cohen, M. (1989) Human endogenous proviruses. Curr. Top. Microbiol. Immunol., v. 148, 115-132.

4. Leib-Mosch, C., Brack-Werner, R., Werner, T., Bachmann, M., Faff, O., Erfle, V. and Hehlmann, R. (1990) Endogenous retroviral elements in human DNA. Cancer Res., v. 50 suppl., 5636s-5642s.

5. Cohen, M. and Larsson, E. (1988) Human endogenous retroviruses. Bioessays, v. 9, 191196.

6. Larsson, E. and Andersson, G. (1998) Beneficial role of human endogenous retroviruses: facts and hypotheses. Scand. J. Immunol., v. 48, 329-338.

7. Lower, R., Lower, J. and Kurth, R. (1996) The viruses in all of us: Characteristics and biological significance of human endogenous retrovirus sequences. Proc. Natl. Acad. Sci. USA, v. 93, 5177-5184.

8. Patience, C., Wilkinson, D.A. and Weiss, R.A. (1997) Our retroviral heritage. Trends Genet., 13,116-120.

9. Sverdlov, E.D. (1998) Perpetually mobile footprints of ancient infections in human genome. FEBSLett., v. 428, 1-6.

10. Harris, J.R. (1998) Placental endogenous retrovirus (ERV): structural, functional, and evolutionary significance. Bioessays, v. 20, 307-316.

11. Leib-Mosch, C. and Seifarth, W. (1995) Evolution and biological significance of human retroelements. Virus Genes, v. 11, 133-145

12. Kim, A., Terzian, C., Santamaria, P., Pelisson, A., Prud'homme, N. and Bucheton, A. (1994) Retroviruses in invertebrates: the gypsy retrotransposon is apparently an infectious retrovirus of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA, v. 91, 1285-1289.

13. Albertola, T.M. and de Frutos, R. (1996) Molecular structure of a gypsy element of Drosophila subobscura (gypsyDs) constituting a degenerate form of insect retroviruses. Nucleic Acids Res., v. 24, 914-923.

14. Bonner, T.I., O'Connell, C. and Cohen, M. (1982) Cloned endogenous retroviral sequences from human DNA. Proc. Natl. Acad. Sci. USA, v. 79, 4709-4713.

15. Perl, A., Rosenblatt, J.D., Chen, I.S.Y., Di Vincenzo, J.P., Bever, R., Poiesz, B.J. and Abraham, G.N. (1989) Detection and cloning of new HTLV-related endogenous sequences in man. Nucleic Acids Res., v. 17, 6841-6854.

16. O'Connel, C., O'Brien, S., Nash, W. and Cohen, M. (1984) ERV3, a full-length human endogenous provirus: chromosomal localization and evolutionary relationships. Virology, v. 138, 225-235.

17. Repaske, R., Steele, P.E., O'Neill, R.R., Rabson, A.B. and Martin, M.A. (1985) Nucleotide sequence of a full-length human endogenous retroviral segment. J.Virol., v. 54, 764-772.

i*

18. Leib-Mosch, C., Brack, R., Werner, T., Erfle, V. and Hehlmann, R. (1986) Isolation of an SSAV-related endogenous sequence from human DNA. Virology, v. 155, 666-676.

19. Mager, D. and Freeman, J. (1987) Human endogenous retrovirus-like genome with type C pol sequences and gag sequences related to human T-cell lymphotropic viruses. J. Virol., v .61, 4060-4066.

20. Kroger, B. and Horak, I. (1987) Isolation of novel human retro virus-related sequences by hybridization to synthetic oligonucleotides complementary to the tRNAPro primer-binding site. J. Virol, v. 61, 2071 -2075.

21. Harada, F., Tsukada, N. and Kato, N. (1987) Isolation of three kinds of human endogenous retrovirus-like sequences using tRNAPro as a probe. Nucleic Acids Res., v. 15, 91539162.

22. Maeda, N. (1985) Nucleotide sequence of the haptoglobin and haptoglobin-related gene pair. The haptoglobin-related gene contains a retrovirus-like element. J. Biol. Chemv. 260, 6698-6709.

23. Brosius, J. and Gould, S.J. (1992) On "genomenclature": a comprehencive (and respectful) taxonomy for pseudogenes and other "junk DNA". Proc. Natl. Acad Sci. USA, v. 89, 10706-10710.

24. Ono, M., Yasunaga, T., Miyata, T. and Ushikubo, H. (1986) Nucleotide sequence of human endogenous retrovirus genome related to the mouse mammary tumor virus genome. J. Virol, v. 60, 589-598.

25. Tassabehji, M., Strachan, T., Anderson, M., Campbell, R.D., Collier, S. and Lako, M. (1994) Identification of a novel family of human endogenous retroviruses and characterization of one family member, HERV-K(C4), located in the complement C4 gene cluster. Nucleic Acids Res., v. 22, 5211-5217.

26. Cordonnier, A., Casella, J.-F. and Heidemann, T. (1995) Isolation of novel human endogenous retrovirus-like elements with foamy virus-related pol sequence. J. Virol, v. 69, 5890-5897.

27. La Mantia, G., Maglione, D., Pengue, G., Di Cristofano, A., Simeone, A., Lanfrancone, L. and Lania, L. (1991) Identification and characterization of novel human endogenous retroviral sequences preferentially expressed in undifferentiated embryonal carcinoma cells. Nucleic Acids Res,, v. 19, 1513-1520.

28. Kjellman, C., Sjogren, H.-O. and Widegren, B. (1995) The Y chromosome: a grveyard for endogenous retroviruses. Gene, v. 161, 163-170.

29. Leib-Mosch, C., Haltmeier, M., Werner, T., Geigl, E.-M., Brack-Werner, R., Francke, U., Erfle, V. and Hehlmann, R. (1993) Genomic distribution and transcription of solitary HERV-K LTRs. Genomics, v. 18, 261-269.

30. Shen, L., Wu, L., Sanlioglu, S., Chen, R., Mendoza, A.R., Dangel, A.W., Carroll, M.C., Zipf, W.B. and Yu, C.Y. (1994) Structure and genetics of the partially duplicated gene RP located immediately upstream of the complement C4A and the C4B genes in the HLA class III region. J. Biol. Chem., v. 269, 8466-8476.

31. Ono, M., Kawakami, M. and Takezawa, T. (1987) A novel human nonviral retroposon derived from an endogenous retrovirus. Nucleic Acids Res., v. 15, 8725-8737.

32. Steinhuber, S., Brack, M., Hunsmann, G., Schwelberger, H., Dierich, M.P. and Vogetse-der, W. (1995) Distribution of human endogenous retrovirus HERV-K genomes in human and different primates. Hum. Genet., v. 96, 188-192.

33. Mager, D.L. and Freeman, J.D. (1995) HERV-H endogenous retroviruses: presence in the New World branch but amplification in the Old World primate lineage. Virology, v. 213, 395404.

34. Goodchild, N.L., Wilkinson, D.A. and Mager, D.L. (1993) Recent evolutionary expansion of a subfamily of RTVL-H human endogenousm retrovirus-like elements. Virology, v. 196, 778-788.

35. Mariani-Costantini, R., Horn, T.M. and Callahan, R. (1989) Ancestry of a human endogenous retrovirus family../. Virol., v. 63, 4982-4985.

36. Shih, A., Coutavas, E.E. and Rush, M.G. (1991) Evolutionary implications of primate endogenous retroviruses. Virology, v. 182, 495-502.

37. Martin, M., Bryan, T., Rasheed, S. and Khan, A. (1981) Identification and cloning of endogenous retroviral sequences present in human DNA. Proc. Natl. Acad. Sci. USA, v. 78, 4892-4896.

38. Repaske, R., O'Neill, R., Steele, P. and Martin, M. (1983) Characterization of partial nucleotide sequence of endogenous type C retrovirus segments in human chromosomal DNA. Proc. Natl. Acad. Sci. USA, v. 80, 678-682.

39. Steel, P., Rabson, A., Bryan, T. and Martin, M. (1984) Distinctive termini characterize two families of human endogenous retroviral sequences. Science, v. 225, 943-947.

40. Silver, J., Rabson, A., Bryan, T., Willey, R. and Martin, M.A. (1987) Human retroviral sequences on the Y chromosome. Mol. Cell. Biol., v. 7, 1559-1562.

41. Emi, M., Horii, A., Tomita, N, Nishide, T., Ogawa, M., Mori, T. and Matsubara, K. (1988) Overlapping two genes in human DNA: a salivary amylase gene overlaps with a gamma-actin pseudogene that carries an integrated human endogenous retroviral DNA. Gene, v. 62, 229-235.

42. Yeh, K.-W., Yang, W.K., Huang, H.-C., Feng, Y.-N, Liu, J.-C., Wu, F.Y.-H. and Wu, C-W. (1995) Cloning and characterization of the endogenous retroviral-tRNAGlu multigene family from human genomes of different racial backgrounds. Gene, v. 155, 247-252.

43. Rabson, A.B., Hamagishi, Y., Steele, P.E., Tykocinski, M. and Martin, M.A. (1985) Characterization of human endogenous retroviral envelope RNA transcripts. J. Virol., v. 56, 176182.

44. Rabson, A., Steel, P., Garos, C. and Martin, M. (1983) mRNA transcripts related to full-length endogenous retroviral DNA in human cells. Nature, v. 306, 604-607.

45. Tomita, N., Horii, A., Doi, S., Yokouchi, H., Ogawa, M., Mori, T. and Matsubara, K. (1990) Transcription of human endogenous retroviral long terminal repeat (LTR) sequence in a lung cancer cell line. Biochem. Biophys. Res. Commun., v. 166, 1-10.

46. O'Connel, C. and Cohen, M. (1984) The LTR sequences of a novel human endogenous retrovirus. Science, v. 226, 1204-1206.

47. Cohen, M., Powers, M., O'Connell, C. and Kato, N. (1985) Nucleotide sequence of the env gene from the human provirus ERV3 and isolation and characterization of an ERV3-specific cDNA. Virology, v. 147, 449-458.

48. Kato, N, Pfeifer-Ohlsson, S., Kato, M., Larsson, E., Rydnert, J., Ohlsson, R. and Cohen, M. (1987) Tissue-specific expression of human provirus ERV3 mRNA in human placenta: two of three ERV3 mRNAs contain human cellular sequences. J. Virol., v. 61, 2182-2191.

49. Kato, N, Shimotohno, K., VanLeeuwen, D. and Cohen, M. (1990) Human proviral mRNAs down regulated in choriocarcinoma encode a zinc finger protein related to Kruppel. Mol. Cell. Biol., v. 10, 4401-4405.

50. Boyd, M.T., Bax, C.M.R., Bax, B.E., Bloxam, D.L. and Weiss, R.A. (1993) The human endogenous retrovirus ERV-3 is upregulated in differentiating placental trophoblast cells. Virology, v. 196, 905-909.

51. Venables, P.J.W., Brookes, S.M., Griffiths, D„ Weiss, R.A. and Boyd, M.T. (1995) Abundance of an endogenous retroviral envelope protein in placental trophoblasts suggests a biological function. Virology, v. 211, 589-592.

52. O'Brien, S.J., Bonner, T.I., Cohen, M., O'Connel, C. and Nash, W.G. (1983) Mapping of an endogenous retroviral sequence to human chromosome 18. Nature, v. 303, 74-77.

53. Renan, M.J. and Reeves, B.R. (1987) Chromosomal localization of human endogenous retroviral element ERV1 to 18q22-q23 by in situ hybridization. Cytogenet. Cell Genet., v. 44, 167-170.

54. La Mantia, G., Pengue, G., Maglione, D., Pannuti, A., Pascucci, A. and Lania, L. (1989) Identification of new human repetitive sequences: characterization of the corresponding cDNAs and their expression in embryonal carcinoma cells. Nucleic Acids Res., v. 17, 59135922.

55. Lania, L., Di Cristofano, A., Strazzulo, M., Pengue, G., Majello, B. and La Mantia, G. (1992) Structural and functional organization of the human endogenous retroviral ERV9 sequences. Virology, v. 191, 464-468.

56. La Mantia, G., Majello, B., Di Cristofano, A., Strazzulo, M., Minchiotti, G. and Lania, L. (1992) Identification of regulatory elements within the minimal promoter region of the human

endogenous ERV9 proviruses: accurate transcription initiation is controlled by an Inr-like element. Nucleic Acids Res., v. 20, 4129-4136.

57. Di Cristofano, A., Strazzulo, M., Longo, L. and La Mantia, G. (1995) Characterization and genomic mapping of the ZNF80 locus: expression of this zinc-finger gene is driven by a solitary LTR ofERV9 endogenous retroviral family. Nucleic Acids Res., v. 23, 2823-2830.

58. Strazzulo, M., Parisi, T., Di Cristofano, A., Rocchi, M. and La Mantia, G. (1998) Characterization and genomic mapping of chimeric ERV9 endogenous retrovirus-host gene transcripts. Gene, v. 206, 77-83.

59. Di Cristofano, A., Strazzulo, M., Parisi, T. and La Mantia, G. (1995) Mobilization of an ERV9 human endogenous retroviral element during primate evolution. Virology, v. 213, 271275.

60. Brack-Werner, R., Barton, D.E., Werner, T., Foellmer, B.E., Leib-Mosch, C., Francke, U., Erfle, V. and Hehlmann, R. (1989) Human SSAV-related endogenous retroviral element LTR-like sequences and chromosomal localization to 18q21. Genomics, v. 4, 68-75.

61. Werner, T„ Brack-Werner, R., Leib-Mosch, C., Backhaus, H., Erfle, V. and Hehlmann, R. (1990) S71 is a phylogenetic distinct human endogenous retroviral element with structural and sequence homology to simian sarcoma virus (SSV). Virology, v. 155, 225-238.

62. Haltmeier, M., Seifarath, W„ Blusch, J., Erfle, V., Hehlmann, R. and Leib-Mosch. (1995) Identification of S71-related human endogenous retroviral sequences with full-length pol genes. Virology, v. 209, 550-560.

63. Noda, M., Kurihara, M. and Takano, T. (1982) Retrovirus-related sequences in human DNA: detection and cloning of sequences which hybridize with the long terminal repeat of baboon endogenous virus. Nucleic Acids Res., v. 10, 2865-2878.

64. Mager, D. and Henthron, P. (1984) Identification of a retrovirus-like repetitive element in human DNA. Proc. Natl. Acad. Sci. USA, v. 81, 7510-7514.

65. Fraser, C., Humphries, R. and Mager, D. (1988) Chromosomal distribution of the RTVL-H family of human endogenous retrovirus-like sequences. Genomics, v. 2, 280-287.

66. Hirose, Y., Takamatsu, M. and Harada, F. (1993) Presence of env genes in members of the RTVL-H family of human endogenous retrovirus like elements. Virology, v. 192, 52-61.

67. Lower, R., Lower, J., Tondera-Koch, C. and Kurth, R. (1993) A general method for the identification of transcribed retrovirus sequences (R-U5 PCR) reveals the expression of the human endogenous retrovirus loci HERV-H and HERV-K in teratocarcinoma cells. Virology, v. 192, 501-511.

68. Wilkinson, D.A., Goodchild, N.L., Saxton, T.M., Wood, S. and Mager, D.L. (1990) Autonomous expression of RTVL-H endogenous retroviruslike elements in human cells. J. Virol., v. 64, 2157-2167.

69. Liu, A.Y. and Abraham, B.A. (1991) Subtractive cloning of a hybrid human endogenous retrovirus and calbindine gene in the prostate cell line PC3. Cancer Res., v. 51, 4107-4110.

70. Baban, S., Freeman, J.D. and Mager, D.L. (1996) Transcripts from a novel human KRAB zinc finger gene contain spliced Alu and endogenous retroviral segments. Genomics, v. 33, 463-472.

71. Kelleher, C.A., Wilkinson, D.A., Freeman, J.D., Mager, D.L. and Gelfand, E.W. (1996) Expression of novel transposon-containing mRNAs in human T cells. J. Gen. Virol., v. 77, 1101-1110.

72. Nelson, D.T., Goodchild, N.L. and Mager, D.L. (1996) Gain of Spl sites and loss of repressor sequences associated with a young, transcriptionally active subset of HERV-H endogenous long terminal repeats. Virology, v. 220, 213-218.

73. Mager, D.L. (1989) Polyadenylation function and sequence variability of the long terminal repeats of the human endogenous retrovirus-like family RTVL-H. Virology, v. 173, 591599.

74. Goodchild, N.L., Wilkinson, D.A. and Mager D.L. (1992) A human endogenous long terminal repeat provides a polyadenylation signal to a novel, alternatively spliced transcript in normal placenta. Gene, v. 121, 287-294.

75. Perl, A., Isaacs, C.M., Eddy, R.L., Byers, M.G. and Shows, T.B. (1991) The human T-cell leukemia virus-related endogenous sequence (HRES1) is located on chromosome 1 at q42. Genomics, v. 11, 1172-1173.

76. Banki, K., Maceda, J., Hurley, E., Ablonczy, E., Mattson, D.H., Szegedy, L., Hung, C. and Perl, A. (1992) Human T-cell lymphotropic virus (HTLV)-related endogenous sequence, HRES-1, encodes a 28-kDa protein: a possible autoantigen forHTLV-I gag-reactive autoantibodies. Proc. Natl. Acad. Sci. USA, v. 89, 1939-1943.

77. Shih, A., Misra, R. and Rush, M.G. (1989) Detection of multiple, novell reverse transcriptase coding sequences in human nucleic asids: relation to primate retroviruses. J. Virol., v. 63, 64-75.

78. Bohannon, R.C., Donehower, L.A. and Ford, R.J. (1991) Isolation of a type D retrovirus from B-cell lymphomas of a patient with AIDS. J. Virol., v. 65, 5663-5672.

79. Donehower, L.A., Bohannon, R.C., Ford, R.J. and Gibbs, R.A. (1990) The use of primers from highly coserved pol regions to identify uncharacterized retrovirus by the polymerase chain reaction. J. Virol. Methods, v. 28, 33-46.

80. Westley, B. and May, F.E.B. (1984) The human genome contains multiple sequences of varying homology to mouse mammary tumor virus DNA. Gene, v. 28, 221-227.

81. May, F., Westley, B„ Rochefort, H„ Buetti, E. and Diggelmann, H. (1983) Mouse mammary tumor virus sequences are present in human DNA. Nucleic Acids Res., v. 11, 41274139.

82. Callahan, R„ Drohan, W., Tronick, S. and Schlom, J. (1982) Detection and cloning of human DNA sequences related to the mouse mammary tumor virus genome. Proc. Natl. Acad. Sci. USA, v. 79, 5503-5507.

83. Callahan, R., Chiu, I.-M., Wong, J., Tronick, S„ Roe, B., Aaronson, S. and Schlom, J. (1985) A new class of endogenous human retroviral genome. Science, v. 228, 1208-1211.

84. Deen, K. and Sweet, R. (1986) Murine mammary tumor virus pol-related sequences in human DNA: characterization and sequnce comparison with the complete murine mammary tumor virus pol gene. J. Virol., v. 57, 422-432.

85. Ono, M. (1986) Molecular cloning and long terminal sequnces of human endogenous retrovirus related to types A and B retrovirus genes. J. Virol., v. 58, 937-944.

86. Li, M.D., Lemke, T.D., Bronson, D.L. and Faras, A.J. (1996) Synthesisand analysis of a 640-bp pol region of novel human endogenous retroviral sequences and their evolutionary relationships. Virology, v. 217, 1-10.

87. Liu, Q.-R. and Chan, P.K. (1990) Identification of a long stretch of homopurine-homopyrimidine sequence in a cluster of retroposons in the human genome. J. Mot Biol, v. 212, 453-459.

88. Kambhu, S., Falldorf, P. and Lee, J.S. (1990) Endogenous retroviral long terminal repeats within the HLA-DQ locus. Proc. Natl. Acad. Sci. USA, v. 87, 4927-4931.

89. Maghsoudlou, S.S., Hughes, T.R. and Hornsby, P.J. (1995) Analysis of the distal 5' region of the human CYP17 gene. Genome, v. 38, 845-849.

90. Li, M.D., Bronson, D.L., Lemke, T.D. and Faras, A.J. (1995) Restricted expression of new HERV-K members in human teratocarcinoma cells. Virology, v. 208, 733-741.

91. Lower, R., Boiler, K., Hasenmaier, B., Korbmacher, C., Mueller-Lantzsch, N., Lower, J. and Kurth, R. (1993) Identification of human endogenous retroviruses with complex mRNA expression and particle formation. Proc. Natl. Acad. Sci. USA, v. 90, 4480-4484.

92. Ono, M., Kawakami, M. and Ushikubo, H. (1987) Stimulation of expression of the human endogenous retrovirus genome by female steroid hormones in human breast cancer cell line T47D. J. Virol., v. 61, 2059-2062.

93. Brodsky, I., Foley, B., Haines, D., Johnston, J., Cuddy, K. and Gillespie, D. (1993) Expression of HERV-K proviruses in human leukocytes. Blood, v. 81, 2369-2374.

94. Medstrand, P., Lindeskog, M. and Blomberg, J. (1992) Expression of human endogenous sequences in peripheral blood mononuclear cells of healthy individuals. J. Gen. Virol., v. 73, 2463-2466.

95. Brodsky, 1., Foley, B. and Gillespie, D. (1993) Expression of human endogenous retrovirus (HERV-K) in chronic myeloid leukemia. Leuk. Lymphoma, v. 11 suppL, 119s-123s.

96. Medstrand, P. and Blomberg, J. (1993) Characterization of novel reverse transcriptase encoding human endogenous retroviral sequences similar to type A and type B retroviruses: differential transcription in normal human tissues../. Virol., v. 67, 6778-6787.

97. Sauter, M., Schommer, S., Kremmer, E., Remberger, K., Dolken, G., Lemm, I., Buck, M., Best, B., Neumann-Haefelin, D. and Mueller-Lantzsch. (1995) Human endogenous retrovirus K10: expression of gag protein and detection of antibodies in patients with seminomas. J. Virol., v. 69, 414-421.

98. Mueller-Lantzsch, N., Sauter, M., Weiskircher, A., Kramer, K., Best, B., Buck, M. and Grasses F. (1993) Human endogenous retroviral element K10 (HERV-K10) encodes a full-length gag homologous 73-kDa protein and a functional protease. AIDS Res. Hum. Retrovirus., v. 9, 343-350.

99. Schommer, S., Sauter, ML, Krausslich, H.-G., Best, B. and Mueller-Lantzsch, N. (1996) Characterization of the human endogenous retrovirus K proteinase. J. Gen. Virol., v. 77, 375379.

Li, Z. and Weissman, S.M. (1993) Application of cDNA selection techniques to regions of the human MHC. Genomics, v. 17, 575-581.

100. Lower, R., Tonjes, R.R., Korbmacher, C., Kurth, R. and Lower, J. (1995) Identification of a Rev-related protein by analysis of spliced transcripts of the human endogenous retroviruses HTDV/HERV-K. J. Virol., v. 69, 141-149.

101. Boiler, K., Konig, H., Sauter, M., Mueller-Lantzsch, N., Lower, R., Lower, J. and Kurth, R. (1993) Evidence that HERV-K is the endogenous retrovirus sequence that codes for the human teratocarcinoma-derived retrovirus HTDV. Virology, v. 196, 349-353.

102. Seifarth, W., Skladny, H., Krieg-Schneider, F., Reichert, A., Hehlmann, R. and LeibMosch, C.J. (1995) Retrovirus-like particles released from the human breast cancer cell line T47-D display type B- and C-related endogenous retroviral sequences. Virology, v. 69, 64086416.

103. Carroll, M.C., Campbell, R.D., Bentley, D R. and Porter, R.R. (1984) A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature, v. 307, 237-241.

104. Yu, C.Y. (1991) The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21-hydroxylase gene. J. Immunol., v. 146, 1057-1066.

105. Seifarth, W., Baust, C, Murr, A., Skladny, H., Krieg-Schneider, F., Blusch, J., Werner, T., Hehlmann, R. and Leib-Mosch, C. (1998) Proviral structure, chromosomal location, and expression of HERV-K-T47D, a novel human endogenous retrovirus derived from T47D particles. J. Virol., v. 72,:8384-8391.

106. Ericson, L.M. and Maeda, N. (1995) A new family of retroviral long terminal repeat elements in the human genome identified by their homologies to an element 5' to the spider monkey haptohlobine gene. Genomics, v. 27, 531-534.

107. Freeh, K., Brack-Werner, R. and Werner, T. (1996) Common modular structure of lenti-virus LTRs. Virology, v. 224, 256-267.

108. Freeh, K., Danescu-Mayer, J. and Werner, T. (1997) A novel method to develop highly specific models for regulatory units detects a new LTR in GenBank which contains a functional promoter. J. Mol. Biol, v. 270, 674-687.

109. Blusch, J.H., Haltmeier, M., Freeh, K., Sander, I., Leib-Mosch, C., Brack-Werner, R. and Werner; T. (1997) Identification of endogenous retroviral sequences based on modular organization: proviral structure at the SSAV1 locus. Genomics, v. 43, 52-61.

110. Jurka, J. (1998) Repeats in genomic DNA: mining and meaning. Curr. Opin. Struct. Biol., v. 8, 333-337.

111. Smit, A.F. A. (1996) The origin of interspersed repeats in the human genome. Curr. Opin. Genet. Dev., V. 6, 743-748.

112. Repbase Update, http://www.girinst.org/Repbase_Update.html

113. Dirksen, E. and Levy, J. (1977) Virus-like particles in placentas from normal individuals and patients with systemic lupus erythematosus../. NCI, v. 59, 1187-1192.

114. Boiler, K., Frank, H., Lower, J., Lower, R. and Kurth, R. (1983) Structural organization of unique retrovirus-like particles budding from human teratocarcinoma cell lines. J. Gen. Virol., v. 64, 2549-2559.

115. Bronson, D., Saxinger, W., Ritzi, D. and Fraley, E. (1984) Production of virions with retrovirus morphology by human embryonal carcinoma cells in vitro. J. Gen. Virol., v. 65, 10431051.

116. Larsson, E., Nilsson, O., Sundstrom, P. and Widehn, S. (1981) Morphological and microbiological signs of endogenous C-virus in human oocytes. Int. J. Cancer, v. 28, 551-557.

117. Juang, S.-H., Huang, J., Li, Y., Salas, P.J.I., Fregien, N., Carothers Carraway, C.A. and Carraway, K.L. (1994) Molecular cloning and sequencing of a 58-kDa membrane- and microfilament associated protein from ascites tumor cell microvilli with sequence similarities to retroviral gag proteins../. Biol. Chem., v. 269, 15067-15075.

118. McDougall, A.S., Terry, A., Tzavaras, T., Cheney, C., Rojko, J. and Neil, J.C. (1994) Defective endogenous proviruses are expressed in feline lymphoid cells: evidence for a role in natural resistance to subgroup B feline leukemia viruses. J. Virol., v. 68, 2151-2160.

119. Krieg, A.M., Gourley, M.F. and Perl, A. (1992) Endogenous retroviruses: potential etio-logic agents in autoimmunity. FASEB J., v. 6, 2537-2544.

120. Perl, A. and Banki, K. (1993) Human endogenous retroviral elements and autoimmunity: data and concepts. Trends Microbiol., v. 1, 153-156.

121. Query, C.C. and Keene, J.D. (1987) A human autoimmune protein associated with U1 RNA contains a region of homology that is cross reactive with retroviral p30gag antigen. Cell, v. 51, 211-220.

122. Mellors, R.C. and Mellors, J.W. (1976) Antigen related to mammalian type-C RNA viral p30 proteins is located in renal glomeruli in human systemic lupus erythematosus. Proc. Natl. Acad. Sci. USA, v. 73, 233-237.

123. Mellors, R.C. and Mellors, J.W. (1978) Type C RNA virus-specific antibody in human systemic lupus erythematosus demonstrated by enzymoimmunoassay. Proc. Natl. Acad. Sci. USA, v. 75, 2463-2467.

124. Rucheton, M., Graafland, H., Fanton, H., Ursule, L., Ferrier, P. and Larsen, C.J. (1985) Presence of circulating antibodies against gag-gene MuLV proteins in patients with autoimmune connective tissue disoders. Virology, v. 144, 468-480.

125. Towler, E.M., Gulnik, S.V., Bhat, T.N., Xie, D„ Gustschina, E., Sumpter, T.R., Robertson, N.,.Jones, C., Sauter, M., Mueller-Lantzsch, N., Debouck, C. and Erickson J.W. (1998) Functional characterization of the protease of human endogenous retrovirus, K10: Can it complement HIV-1 protease? Biochemistry, v. 37, 17137-17144.

126. Conrad, B., Weissmahr, R.N., Boni, J., Arcari, R., Schupbach, J. and Mach, B. (1997) A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes. Cell, v.90, 303-313.

127. Murhy, V.J., Harrison, L.C., Rudert, W.A., Luppi, P., Trucco, M., Fierabracci, A., Biro, P.A. and Bottazzo, G.F. (1998) Retroviral superantigens and type 1 diabetes mellitus. Cell, v. 95, 9-11.

128. Lower, R., Tonjes, R.R., Boiler, K., Denner, J., Kaiser, B., Phelps, R.C., Lower, J., Kurth, R., Badenhoop, K., Donner, H., Usadel, K.H., Miethke, T., Lapatschek, M. and Wagner, H. (1998) Development of insulin-dependent diabetes mellitus does not dependent on specific expression of the human endogenous retrovirus HERV-K. Cell, v. 95, 11-14.

129. Lan, M.S., Mason, A., Coutant, R., Chen, Q.-Y., Vargas, A., Rao, J., Gomez, R., Chalew, S., Garry, R. and Maclaren, N.K. (1998) HERV-KlOs and immune-mediated (type 1) diabetes. Cell, v. 95, 14-16.

130. Medstrand, P. and Mager, D.L. (1998) Human-Specific Integrations of the HERV-K Endogenous Retrovirus Family. J. Virol., v. 72, 9782-9787.

131. Berlioz, C., Torrent, C. and Darlix, J.-L. (1995) An internal ribosomal entry signal in the rat VL30 region of the Harvey murine sarcoma virus leader and its use in dicistronic retroviral vectors. J. Virol, v. 69, 6400-6407.

132. Estes, S.D., Stoler, D.L. and Anderson, G.R. (1995) Anoxic induction of a sarcoma virus-related VL30 retrotransposon is mediated by a cis-acting element which binds hypoxia-inducible factor 1 and an anoxia-inducible factor. J. Virol, v. 69, 6335-6341.

133. Cho, K., Ferrick, D.A. and Morris, D.W. (1995) Structure and biological activity of the subgenomic Mtv-6 endogenous provirus. Virology, v. 206, 395-402.

134. Lindeskog, M., Medstrand, P., Cunningham, A.A. and Blomberg, J. (1998) Coamplifi-cation and dispersion of adjacent human endogenous retroviral HERV-H and HERV-E elements; presence of spliced hybrid transcripts in normal leukocytes. Virology, v. 244, 219-229.

135. Pesce, G.C., Rossi, M.S., Muro, A.F., Reig, O.A., Zorzopulos, J. and Kornblihtt, A.R. (1994) Binding of nuclear factors to a satellite DNA of retroviral origin with marked difference in copy number among species of rodent Ctenomys. Nucleic Acids Res., v. 22, 656-661.

136. Shih, C., Stoye, J.P. and Coffin, J.M. (1988) Highly preferred targets for retrovirus integration. Cell, v. 53, 531-537.

137. Vijaya, S., Steffen, D.L. and Robinson, H.L. (1986) Acceptor sites for retroviral integration map near DNase I-hypersensitive sites in chromatin. J. Virol., v. 60, 683-692.

138. Curcio, M.J. and Morse, R.H. (1996) 'Tying together integration and chromatin. Trends Genet., v. 12, 436-438.

139. Bor, Y.-C., Miller, M.D., Bushman, F.D. and Orgel, L.E. (1996) Target-sequence preferences of HIV-1 integration complexes in vitro. Virology, v. 222, 283-288.

140. Kelley, M R., Kidd, S., Berg, R.A. and Young, M.W. (1987) Restriction of P-element insertions at the Notch locus of Drosophila melanogaster. Mol. Cell. Biol., v. 7, 1545-1548.

141. Swift, R.A., Shaller, E., Witter, R.L. and Kung, H.-J. (1985) Insertional activation of c-myc by reticuloendotheliosis virus in chiken B lymphoma: nonrandom distribution and orientation of the proviruses. J. Virol., v. 54, 869-872.

142. Huang, H„ Qian, J., Proffi, J., Wilber, K., Jenkins, R. and Smith, D.I. (1998) FRA7G extends over a broad region: coincidence of human endogenous retroviral sequences (HERV-H) and small polydispersed circullar DNAs (spcDNA) and fragile sites. Oncogene, v. 16, 2311-2319.

143. Herman, S.A. and Coffin, J.M. (1986) Differential transcription from the long terminal repeats of integrated avian leukosis virus DNA. J. Virol., v. 60, 497-505.

144. Sosa, M.A.G., Rosas, D.H., DeGasperi, R., Morita, E., Hutchison, M.R. and Ruprecht, R.M. (1994) Negative regulation of the 5' long terminal repeat (LTR) by the 3' LTR in the murine proviral genome. J. Virol, v. 68, 2662-2670.

145. Winslow, B.J., Pomerantz, R.J., Bagasara, O. and Trond, D. (1993) HIV-1 latency due to the site of proviral integration. Virology, v. 196, 849-854.

146. Makalowski, W., Mitchell, G.A. and Labuda, D. (1994) Alu sequences in the coding regions of mRNA: a source of protein variability. Trends Genet., v. 10, 188-193.

147. Banki, K., Halladay, D. and Perl, A. (1994) Cloning and expression of the human gene for transaldolase. A novel highly repetitive element constitutes an integral part of the coding sequence. J. Biol. Chem., v. 269, 2847-2851.

148. Kawamoto, S., Ilashizume, S., Katakura, Y., Tachibana, H. and Murakami, H. (1995) Molecular cloning of yeast cytochrome c-like polypeptide expressed in human lung carcinoma: an antigen recognizable by lung cancer-specific human monoclonal antibody. In Vitro Cell. Dev. Biol.-Animal, v. 31, 724-729.

149. Kapitonov, V.V. and Jurka, J. (1999) The long terminal repeat of an endogenous retrovirus induces alternative splicing and encodes an additional carboxy-terminal sequence in the human leptin receptor../. Mol. Evol, v. 48, 248-251.

150. Choi, Y., Kappler, J.W. and Marrack, P. (1991) A superantigene encoded in the open reading frame of the 3' long terminal repeat of mouse mammary tumor virus. Nature, v. 350, 203-207.

151. Suzuki, H., Hosokawa, Y., Toda, H., Nishikimi, M. and Ozawa, T. (1990) Common protein^binding sites in the 5'-flanking regions of human genes for cytochrome cl and ubiqui-none-binding protein. J. Biol Chem., v. 265, 8159-8163.

152. Feuchter-Murthy, A.E., Freeman, J.D. and Mager, D.L. (1993) Splicing of a human endogenous retrovirus to a novel phospholipase A2 related gene. Nucleic Acids Res., v. 21, 135143.

153. Feuchter, A., Freeman, J.D. and Mager, D.L. (1992) Strategy for detecting cellular transcripts promoted by human endogenous long terminal repeats: identification of a novel gene (CDC4L) with homology to yeast CDC4. Genomics, v. 13, 1237-1245.

154. Ting, C.N., Rosenberg, M.P., Snow, C.M., Samuelson, L.C. and Meisler, M.H. (1992) Endogenous retroviral sequences are required for tissue-specific expression of a human salivary amylase gene. Genes Dev., v. 6, 1457-1465.

155. Connelly, M.A., Grady, R.C., Mushinski, J.F. and Marcu, K.B. (1994) PANG, a gene encoding a neuronal glycoprotein, is ectopically activated be intracisternal A-particle long terminal repeats in murine plasmacytomas. Proc. Natl Acad. Sci. USA, v. 91, 1337-1341.

156. Canaani, E., Dreazen, O., Klar, A., Rechavi, G., Ram, D., Cohen, J.B. and Givol, D. (1983) Activation of the c-mos oncogene in a mouse plasmacytoma by insertion of an endogenous intracisternal A-particle genome. Proc. Natl. Acad. Sci. USA, v. 80, 7118-7122.

157. Madhusudhan, K.T., Naik, S.S. and Patel, M.S. (1995) Characterization of the promoter regulatory region of the human pyruvate dehydrogenase gene. Biochemistry, v. 34, 12881294.

158. GenBank Accession D90086.

159. Britten, R.J. (1997) Mobile elements inserted in the distant past have taken on important functions. Gene, v. 205, 177-182.

160. Britten, R.J. (1996) DNA sequence insertion and evolutionary variation in gene regulation. Proc. Natl Acad. Sci. USA, v. 93, 9374-9377.

161. Britten, R.J. (1996) Cases of ancient mobile element DNA insertions that now affect gene regulation. Mol. Phylogenet. Evol, v. 5, 13-17.

162. Choi, S.Y. and Faller, D.V. (1994) The long terminal repeats of a murine retrovirus encode a trans-activator for cellular genes. J. Biol Chem., v. 269, 19691-19694.

163. Weng, H., Choi, S.Y. and Faller, D.V. (1995) The Moloney leukemia retroviral long terminal repeat trans-activates AP-1-inducible genes and AP-1 transcription factor binding. J. Biol Chem., v. 270, 13637-13644.

164. Choi, S.-Y. and Faller, D.V. (1995) A transcript from the long terminal repeats of a murine retrovirus associated with trans activation of cellular genes. J. Virol, v. 69, 70547060.

165. Hao, Y., Crenshaw, T., Moulton, T., Newcomb, E. and Tycko, B. (1993) Tumor-suppresor activity of H19 RNA. Nature, v. 365, 764-767.

166. Rastinejad, F. and Blau, H.M. (1993) Genetic complementation reveals a novel regulatory role for 3' untranslated regions in growth and differentiation. Cell, v. 72, 903-917.

167. Volik, S„ Lebedev, Y., Nikolaev, L., Shevchenko, Y., Vinogradova, T., Kopantzev, E., Kolesnik, T., Monastyrskaya, G., Kunz, U., Grzeschik, K.-H., Ashworth, L.K., Lennon, G. and Sverdlov, E. (1995) Mapping of transcribed sequences on human chromosome 19. DNA Seq., v. 6, 13-26.

168. Lebdev, Y.B., Volik, S.V., Obradovic, D., Ermolaeva, O.D., Ashworth, L.K., Lennon, G.G. and Sverdlov, E.D. (1995) Physical mapping of sequences, homologous to an endogenous retrovirus LTR on human chromosome 19. Mo I Gen. Genet., v. 247, 742-748.

169.Vinogradova, T.V., Shevchenko, Y.O., Lavrenteva, I.V., Khil, P.P., Volik, S.V., Lebedev, Y.B., Ashworth, L.K., Grzeschik, K.-H. and Sverdlov, E.D. (1996) Map of Chr-19 specific transcribed sequences with 300 kb resolution. HGMAbstracts, 103.

170. Lovett, M. (1994) Fishing for complements: finding genes by direct selection. Trends Genet., v. 10, 352-357.

171. Parrish, J.E. and Nelson, D.L. (1993) Methods for finding genes. A major rate-limiting step in positional cloning. Genet. Anal, v. 10, 29-41.

172. Monaco, A.P. (1994) Isolation of genes from cloned DNA. Curr. Opin. Genet. Dev., v. 4, 360-366.

173. Fickett, J.W. (1996) Finding genes by computer: the state of the art. Trends Genet., v. 12, 316-320.

174. Church, D.M, Stotler, C.J., Rutter, J.L., Murrell, J.R., Trofatter, J. A. and Buckler, A.J. (1994) Isolation of genes from complex sources of mammalian genomic DNA using exon amplification. Nature Genet., v. 6, 98-105.

175. Parrish, J.E. and Nelson, D.L. (1993) Methods for finding genes. A major rate-limiting step in positional cloning. Genet. Anal, v. 10, 29-41.

176. Monaco, A.P. (1994) Isolation of genes from cloned DNA. Curr. Opin. Genet. Dev., v. 4, 360-366.

177. Tagle, D.A., Swaroop, M., Lovett, M. and Collins, F.S. (1993) Magnetic bead capture of expressed sequences encoded within large genomic segments. Nature, v. 361, 751-753.

178. Parimoo, S., Patanjali, S.R., Kolluri, R, Xu, H., Wei, H. and Weissman, S.M. (1995) cDNA selection and other approaches in positional cloning. Anal Biochem., v. 228, 1-17.

179. Lovett, M., Kere, J. and Hinton, L.M. (1991) Direct selection: a method for the isolation of cDNAs encoded by large genomic regions. Proc. Natl Acad. Sci. USA, v. 88, 9628-9632.

180. Parimoo, S., Patanjali, S.R., Shukla, H., Chaplin, D.D. and Weissman, S.R. (1991) cDNA selection: efficient PCR approach for the selection of cDNAs encoded'in large chromosomal DNA fragments. Proc. Natl. Acad. Sci. USA, v. 88, 9623-9627.

181. Morgan, J.G., Dolganov, G.M., Robbins, S.E., Hinton, L.M. and Lovett, M. (1992) The selective isolation of novel cDNAs encoded by the regions surrounding the human interleukin 4 and 5 genes. Nucleic Acids Res., v. 20, 5173-5179.

182. Korn, B., Sedlacek, Z., Manca, A., Kioschis, P., Konecki, D., Lehrach, H. and Poustka, A. (1992) A strategy for the selection of transcribed sequences in the Xq28 region. Hum. Molec. Genet., v. 1, 235-242.

183. Bailey, D.M.D., Carter, N.P., de Vos, D., Leveresha, M.A., Perryman, M.T. and Ferguson-Smith, M.A. (1993) Coincidence painting: a rapid method for cloning region specific DNA sequences. Nucleic Acids Res., v. 21, 5117-5123.

184. Das Gupta, R., Morrow, B., Marondel, I., Parimoo, S., Goei, V.L., Gruen, J., Weissman, S., Skoultchi, A. and Kucherlapati, R. (1993) An integrated approach for identifying and mapping human genes. Proc. Natl. Acad. Sci. USA, v. 90, 4364-4368.

185. Brookes, A.J., Slorach, E.M., Evans, K.L., Thomson, M.L., Gosden, C.M., Muir, W.J. and Porteus, D.J. (1995) Identifying genes within microdissected genomic DNA: isolation of brain expressed genes from a translocation region associated with inherited mental illness. Mammal. Genome, v. 6, 257-262.

186. Rouquier, S., Trask, B.J., Taviaux, S., van der Engh, G., Diriong, S., Lennon, G.G. and Giorgi, D. (1995) Direct selection of cDNAs using whole chromosomes. Nucleic Acids Res., v. 23, 4415-4420.

187. Sedlacek, Z., Konecki, D.S., Siebenhaar, R., Kioschis, P. and Poustka, A. (1993) Direct selection of DNA sequences conserved between species. Nucleic Acids Res., v. 21, 34193425.

188. Savitsky, K., Bar-Shira, A., Gilad, S„ Rotman, G„ Ziv, Y., Vanagaite, L„ Tagle, D.A., Smith, S., Uziel, T., Sfez, S., Ashkenazi, M., Pecker, I., Frydman, M., Harnik, R., Patanjali, S.R., Simmons, A., Clines, G.A., Sartiel, A., Gatti, R.A., Chessa, L., Sanal, O., Lavin, M.F., Jaspers, N.G.J., Taylor, A.M.R., Arlett, C.F., Miki, T„ Weissman, S.M., Lovett, M., Collins, F.S. and Shiloh, Y. (1995) A single ataxia telangiectasia gene with product similar to PI-3 kinase. Science, v. 268, 1749-1753.

189. Vetrie, D., Vorechovsky, I., Sideras, P., Holland, J., Davies, A., Flinter, F., Hammar-strom, L., Kinnon, C., Levinsky, R„ Bobrow, M„ Smith, C.I.E. and Bentley, D.R. (1993) The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature, v. 361, 226-233.

190. Derry, J.M.J., Ochs, H.D. and Francke, U. (1994) Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell, v. 78, 635-644.

191. Miki, Y., Swensen, J., Shattuck-Eldens, D., Futreal, P.A., Harshmann, K., Tavtigian, S., Liu, Q., Cochran, C., Bennett, L.M., Ding, W., Bell, R„ Rosenthal, J., Hussey, C., Tran, T., McClure, M., Frye, C., Hattier, T., Phelps, R., Haugen-Strano, A., Katcher, H., Yakumo, K., Gholami, Z., Shaffer, D., Stone, S., Bayer, S„ Wray, C„ Bogden, R., Dayananth, P., Ward, J., Tonin, P., Narod, S., Bristow, P.K., Norris, F.H., Helvering, L., Morrison, P., Rosteck, P., Lai, M., Barrett, J.C., Lewis, C., Neuhausen, S., Cannon-Albright, L., Goldgar, D., Wiseman, R., Kamb, A. and Skolnick, M.H. (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science, v. 266, 66-71.

192. Jou, Y.-S., Goold, R.D. and Myers, R.M. (1994) Localization of the alpha2-macroglobulin receptor-associated protein 1 gene (LRPAP1) and other gene fragments to human chromosome 4pl6.3 by direct cDNA selection. Genomics, v. 24, 410-413.

193. Goldberg, Y.P., Lin, B.-Y., Andrew, S.E., Nasir, J., Graham, R., Glaves, M.L., Hutchinson, G., Theilmann, J., Ginzinger, D.G., Schappert, K., Clarke, L., Rommens, J.M. and Hayden, M.R. (1992) Cloning and mapping of the alpha-adductin gene close to D4S95 and assessment of its relationship to Huntington disease. Hum. Molec. Genet.., v. 1, 669-675.

194. Simmons, A.D., Goodart, S.A., Gallardo, T.D., Overhauser, J. and Lovett, M. (1995) Five novel genes from the cri-du-chat critical region isolated by direct selection. Hum. Molec. Genet., v. 4, 295-302.

195. Fan, W.-F., Wei, X., Shukla, H., Parimoo, S„ Xu, H„ Patanjali, S.R.,

196. Wei, H., Fan, W.-F., Xu, H., Parimoo, S., Shukla, H„ Chaplin, D.D. and Weissman, S.M. (1993) Genes in one megabase of the HLA class I region. Proc. Natl Acad. Sci. USA, v. 90, 11870-11874.

197. Hromas, R., Collins, S.J., Hickstein, D., Raskind, W., Deaven, L.L., O'Hara, P., Hagen, F.S. and Kaushansky, K. (1991) A retinoic acid-responsive human zinc finger gene, MZF-1, preferentially expressed in myeloid cells. J. Biol. Chem., v. 266, 14183-14187.

198. Yulug, I.G., Yulug, A. and Fisher, E.M.C. (1995) The frequency and position of Alu repeats in cDNAs, as determined by database searching. Genomics, v. 27, 544-548.

199. Crew, A.J., Clark, J., Fisher, C., Gill, S„ Grimer, R„ Chand, A., Shipley, J., Gusterson, B.A. and Cooper, C.S. (1995) Fusion of SYTio two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma. EMBO J., x. 14, 2333-2340.

200. Eichler, E.E., Hoffman, S.M., Adamson, A.A., Gordon, L.A., McCready, P., Lamerdin, J.E. and Mohrenweiser, H.W. (1998) Complex p-satellite repeat structures and the expansion of the zinc finger gene cluster in 19pl2. Genome Res., v. 8, 791-808.

201. Bellefroid, E.J., Marine, J.-C., Ried, T., Lecocq, P.J., Riviere, M., Amemiya, C., Ponce-let, D.A., Coulie, P.G., Jong, P., Szipiper, C., Ward, D.C. and Martial, J. (1993) Clustered organization of homologous KRAB zinc-finger genes with enhanced expression in human T lymphoid cells. EMBO J., v. 12, 1363-1374.

202. Bellefroid, E.J., Poncelet, D.A., Lecocq, P.J., Revelant, O. and Martial, J. (1991) The evolutionarily conserved Kruppel-associated box domain defines a subfamily of eukaryotic multifingered proteins. Proc. Natl Acad. Sci. USA, v. 88, 3608-3612.

203. Pengue, G., Calabro, V., Cannada Bartoli, P., Pagliuca, A. and Lania, L. (1994) Repression of transcriptional activity at a distance by the evolutionarily conserved KRAB domain present in a subfamily of zinc finger proteins. Nucleic Acids Res., v. 22, 2908-2914.

204. Bellefroid, E.J., Marine, J.-C., Matera, A.G., Bourguignon, C., Desai, T., Healy, K.C., Bray-Ward, P., Martial, J., Ihle, J.N. and Ward D.C. (1995) Emergence of the ZNF91 Krup-

pel-associated box-containing zinc finger gene family in the last common ancestor of anthro-poidea. Proc. Natl. Acad. Sci. USA, v. 92, 10757-10761.

205. Seperack, P.K., Mercer, J. A., Strobel, M.C., Copeland, N.G. and Jenkins N. A. (1995) Retroviral sequences located within an intron of the dilute gene alter dilute expression in a tissue-specific manner. EMBOJ., v. 14, 2326-2332.

206. Smith, S.W., Overbeek, R., Woese, C.R., Gilbert, W. and Gillevet, P.M. (1994) The genetic data environment: an expandable GUI for multiple sequence analysis. Cotnpul. Appl. Bi-osci., v. 10, 671-675.

207. Matz, M., Shagin, D., Bogdanova, E., Britanova, O., Lukyanov, S., Diatchenko, L. and Chenchik A. (1999) Amplification of cDNA ends based on template-switching effect and step-out PCR. Nucleic Acids Res., in press.

208. Liu, A.Y., Torchia, B.S., Migeon, B.R. and Siliciano, R.F. (1997) The human NTT gene: identification of a novel 17-kb noncoding nuclear RNA expressed in activated CD4+ T cells. Genomics, v. 39, 171-184.

209. Thompson, J.D., Higgins, D.G. and Gibson, T.J. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position specific gap penalties and weight matrix choice. Nucleic Acids Res., v. 22, 4673-4680.

210. Thompson, J. and Jeanmougin, F. (1997) CLUSTAL X Multiple Sequence Alignment Program v. 1.5b. Distributed by the author.

211. Felsenstein, J. (1989) PHYLIP — Phylogeny Inference Package. Cladistics, v. 5, 164166.

212. Nicholas, K.B. and Nicholas, H.B. Jr. (1997) GeneDoc: a tool for editing and annotation multiple sequence alignment. Distributed by the author.

213. Smit, A.F.A., Toth, G., Riggs, A.D. and Jurka, J. (1995) Ancestral, mammalian-wide subfamilies of LINE-1 repetitive sequences. J. Mol. Biol., v. 246, 401-417.

214. Carrano, A.V., de Jong, P.J., Branscomb, E„ Slezak, T. and Watkins, B.W. (1989) Constructing chromosome- and region-specific cosmid maps of the human genome. Genome, v. 31, 1059-1065.

215. Ashworth, L.K., Batzer, M.A., Brandriff, B., Branscomb, E., de Jong, P., Garcia, E., Games, J.A., Gordon, L.A., Lamerdin, J.E., Lennon, G., Mohrenweiser, H., Olsen, A.S., Slezak, T. and Carrano, A.V. (1995) An integrated metric physical map of human chromosome 19. Nature Genet., v. 11, 422-427.

216. Lukyanov, K.A., Matz, M.V., Bogdanova, E.A., Gurskaya, N.G. and Lukyanov, S.A. (1996) Molecule by molecule PCR amplification of complex DNA mixtures for direct sequencing: an approach to in vitro cloning. Nucleic Acids Res., v. 24, 2194-2195.