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Gene Review

HTC2  -  hypertrichosis 2 (generalized, congenital)

Homo sapiens

Synonyms: CGH, CXINSq27.1, HCG
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Disease relevance of HTC2


Psychiatry related information on HTC2

  • Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features [6].
  • Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH [6].
  • As of today, a few hundred iatrogenic cases of CJD have been diagnosed worldwide, the majority due to transmission by cadaveric pituitary HCG [7].

High impact information on HTC2

  • Genome scanning with array CGH delineates regional alterations in mouse islet carcinomas [8].
  • Novel molecular karyotyping methods, such as array-based comparative genomic hybridization (array CGH), can detect submicroscopic chromosome alterations at a resolution of 100 kb [9].
  • Our data demonstrate that it is possible to screen the human genome for copy-number changes with array CGH at a resolution that is 2 orders of magnitude higher than that previously reported [10].
  • We report here a significant improvement in the resolution of array CGH, with the development of an array platform that utilizes single-stranded DNA array elements to accurately measure copy-number changes of individual exons in the human genome [10].
  • To elucidate the molecular structure of these duplication chromosomes, we designed a high-resolution array comparative genomic hybridization (array CGH) platform [11].

Chemical compound and disease context of HTC2


Biological context of HTC2

  • The CGH arrays used in these experiments carried BACs distributed at 2-20-MB intervals across the mouse genome and at higher density in regions of interest [8].
  • High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage [11].
  • Second, we examined the structure and gene expression profile of genomic amplifications involving 18q21 in a panel of 40 B-NHL cell lines using comparative genomic hybridization to microarrays (array CGH) and gene expression profiling techniques [17].
  • Novel genomic technologies such as microarray-based comparative genomic hybridization (array CGH) allow the mapping of genomic copy number alterations at this submicroscopic level, thereby directly linking disease phenotypes to gene dosage alterations [18].
  • All array CGH results agree with the deletion sizes and locations of the breakpoints in these subjects as determined previously by FISH and microsatellite analyses [3].

Anatomical context of HTC2

  • Simultaneously, tryptic digests were used to pulse CBA/J macrophages and tested for their ability to be recognized by HTC2 cells [19].
  • Since T cells recognize degraded forms of the antigen and since endogenous antigens preferentially activate class I-restricted T cells, we hypothesized that one cytotoxic T cell hybridoma, named HTC2, which prevents further EAT induction in mice injected with Tg would be specific for one EAT inducer peptide [19].
  • 12p-amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH [20].
  • Early in vivo studies and more recent CGH analyses have revealed amplification of chromosome 5p in advanced stage carcinoma of the uterine cervix (CaCx) [21].
  • Even more strikingly, 11q deletions, which are present in 20%-30 % of MCL and B-CLL, were found very rarely in other nodal B-cell lymphomas (CGH: 1 of 208 cases; FISH: 1 of 69 cases) [22].

Associations of HTC2 with chemical compounds

  • Fresh frozen and formalin-fixed, paraffin-embedded samples of DFSP were analyzed by array CGH (four cases) and DNA microarray analysis of global gene expression (nine cases) [23].
  • Although three related glycoprotein hormones, LH, hFSH, and hTSH, are secreted by the pituitary, HCG is the only one of this family of glycoprotein hormones that is produced by the placenta in primates to maintain the steroid hormone secretions of the corpus luteum [24].
  • Age, day 2 FSH and FSH ratio were not significantly correlated with oestradiol on HCG day, total follicles and follicles > or = 14 mm [25].
  • Leptin time- and dose-dependently inhibited (P < 0.05) HCG-stimulated progesterone production by human luteinized GC, but did not alter basal steroidogenesis [26].
  • Corpus luteum response to exogenous HCG during the mid-luteal phase of the menstrual cycle [27].

Analytical, diagnostic and therapeutic context of HTC2

  • Here we show that comparative genomic hybridization to DNA microarrays (array CGH) overcomes these limitations by allowing efficient, genome-wide analyses of relative genome copy number [8].
  • In comparison to chromosomal CGH, a 50% higher number of aberrations was found and the high specificity of matrix-CGH was demonstrated by fluorescence in situ hybridization (FISH) analyses [28].
  • Northern blot analysis revealed HIP gene overexpression in all of the human thyroid carcinoma cell lines analyzed, as compared to the HTC 2 cells [5].
  • We have developed a protocol for degenerate oligonucleotide-primed-polymerase chain reaction-based array comparative genomic hybridization (array CGH) that, when combined with a laser microdissection technique, allows the analysis of cancer cell populations isolated from routine, formalin-fixed, paraffin-embedded tissue samples [29].
  • The array CGH method described here will allow the genetic analysis of paraffin-embedded human cancer materials for example in the context of clinical trials [29].


  1. Regional copy number-independent deregulation of transcription in cancer. Stransky, N., Vallot, C., Reyal, F., Bernard-Pierrot, I., de Medina, S.G., Segraves, R., de Rycke, Y., Elvin, P., Cassidy, A., Spraggon, C., Graham, A., Southgate, J., Asselain, B., Allory, Y., Abbou, C.C., Albertson, D.G., Thiery, J.P., Chopin, D.K., Pinkel, D., Radvanyi, F. Nat. Genet. (2006) [Pubmed]
  2. Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Pollack, J.R., Sørlie, T., Perou, C.M., Rees, C.A., Jeffrey, S.S., Lonning, P.E., Tibshirani, R., Botstein, D., Børresen-Dale, A.L., Brown, P.O. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Development of a comparative genomic hybridization microarray and demonstration of its utility with 25 well-characterized 1p36 deletions. Yu, W., Ballif, B.C., Kashork, C.D., Heilstedt, H.A., Howard, L.A., Cai, W.W., White, L.D., Liu, W., Beaudet, A.L., Bejjani, B.A., Shaw, C.A., Shaffer, L.G. Hum. Mol. Genet. (2003) [Pubmed]
  4. Multiple microalterations detected at high frequency in oral cancer. Baldwin, C., Garnis, C., Zhang, L., Rosin, M.P., Lam, W.L. Cancer Res. (2005) [Pubmed]
  5. Overexpression of the HIP gene coding for a heparin/heparan sulfate-binding protein in human thyroid carcinomas. de Nigris, F., Visconti, R., Cerutti, J., Califano, D., Mineo, A., Santoro, M., Santelli, G., Fusco, A. Cancer Res. (1998) [Pubmed]
  6. Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability. Shaw-Smith, C., Pittman, A.M., Willatt, L., Martin, H., Rickman, L., Gribble, S., Curley, R., Cumming, S., Dunn, C., Kalaitzopoulos, D., Porter, K., Prigmore, E., Krepischi-Santos, A.C., Varela, M.C., Koiffmann, C.P., Lees, A.J., Rosenberg, C., Firth, H.V., de Silva, R., Carter, N.P. Nat. Genet. (2006) [Pubmed]
  7. Prion diseases: epidemiology in man. Pedersen, N.S., Smith, E. APMIS (2002) [Pubmed]
  8. Genome scanning with array CGH delineates regional alterations in mouse islet carcinomas. Hodgson, G., Hager, J.H., Volik, S., Hariono, S., Wernick, M., Moore, D., Nowak, N., Albertson, D.G., Pinkel, D., Collins, C., Hanahan, D., Gray, J.W. Nat. Genet. (2001) [Pubmed]
  9. Diagnostic genome profiling in mental retardation. de Vries, B.B., Pfundt, R., Leisink, M., Koolen, D.A., Vissers, L.E., Janssen, I.M., Reijmersdal, S., Nillesen, W.M., Huys, E.H., Leeuw, N., Smeets, D., Sistermans, E.A., Feuth, T., van Ravenswaaij-Arts, C.M., van Kessel, A.G., Schoenmakers, E.F., Brunner, H.G., Veltman, J.A. Am. J. Hum. Genet. (2005) [Pubmed]
  10. Exon array CGH: detection of copy-number changes at the resolution of individual exons in the human genome. Dhami, P., Coffey, A.J., Abbs, S., Vermeesch, J.R., Dumanski, J.P., Woodward, K.J., Andrews, R.M., Langford, C., Vetrie, D. Am. J. Hum. Genet. (2005) [Pubmed]
  11. High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage. Wang, N.J., Liu, D., Parokonny, A.S., Schanen, N.C. Am. J. Hum. Genet. (2004) [Pubmed]
  12. Cytogenetic and expression profiles associated with transformation to androgen-resistant prostate cancer. Pang, S.T., Weng, W.H., Flores-Morales, A., Johansson, B., Pourian, M.R., Nilsson, P., Pousette, A., Larsson, C., Norstedt, G. Prostate (2006) [Pubmed]
  13. Accurate detection of aneuploidies in array CGH and gene expression microarray data. Myers, C.L., Dunham, M.J., Kung, S.Y., Troyanskaya, O.G. Bioinformatics (2004) [Pubmed]
  14. Analysis of DNA in endometrial cancer cells treated with phyto-estrogenic compounds using comparative genomic hybridisation microarrays. O'Toole, S.A., Sheppard, B.L., Sheils, O., O'Leary, J.J., Spengler, B., Christoffel, V. Planta Med. (2005) [Pubmed]
  15. Comparative methodological analysis of erbB-2/HER-2 gene dosage, chromosomal copy number and protein overexpression in breast carcinoma tissues for diagnostic use. Bánkfalvi, A., Simon, R., Brandt, B., Bürger, H., Vollmer, I., Dockhorn-Dworniczak, B., Lellé, R.J., Boecker, W. Histopathology (2000) [Pubmed]
  16. Comparative genomic hybridization study of paraffin-embedded dedifferentiated liposarcoma fixed with Holland Bouin's fluid. Hostein, I., Coindre, J.M., Derré, J., Mariani, O., Chibon, F., Aurias, A. Diagn. Mol. Pathol. (2003) [Pubmed]
  17. MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma. Sanchez-Izquierdo, D., Buchonnet, G., Siebert, R., Gascoyne, R.D., Climent, J., Karran, L., Marin, M., Blesa, D., Horsman, D., Rosenwald, A., Staudt, L.M., Albertson, D.G., Du, M.Q., Ye, H., Marynen, P., Garcia-Conde, J., Pinkel, D., Dyer, M.J., Martinez-Climent, J.A. Blood (2003) [Pubmed]
  18. Identification of disease genes by whole genome CGH arrays. Vissers, L.E., Veltman, J.A., van Kessel, A.G., Brunner, H.G. Hum. Mol. Genet. (2005) [Pubmed]
  19. T cell mapping of one epitope from thyroglobulin inducing experimental autoimmune thyroiditis (EAT). Bedin, C., Brazillet, M.P., Texier, B., Charreire, J. Int. Rev. Immunol. (1992) [Pubmed]
  20. 12p-amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH. Zafarana, G., Grygalewicz, B., Gillis, A.J., Vissers, L.E., van de Vliet, W., van Gurp, R.J., Stoop, H., Debiec-Rychter, M., Oosterhuis, J.W., van Kessel, A.G., Schoenmakers, E.F., Looijenga, L.H., Veltman, J.A. Oncogene (2003) [Pubmed]
  21. Amplification of chromosome 5p correlates with increased expression of Skp2 in HPV-immortalized keratinocytes. Dowen, S.E., Neutze, D.M., Pett, M.R., Cottage, A., Stern, P., Coleman, N., Stanley, M.A. Oncogene (2003) [Pubmed]
  22. t(11;14)-positive mantle cell lymphomas exhibit complex karyotypes and share similarities with B-cell chronic lymphocytic leukemia. Bentz, M., Plesch, A., Bullinger, L., Stilgenbauer, S., Ott, G., Müller-Hermelink, H.K., Baudis, M., Barth, T.F., Möller, P., Lichter, P., Döhner, H. Genes Chromosomes Cancer (2000) [Pubmed]
  23. Gene expression patterns and gene copy number changes in dermatofibrosarcoma protuberans. Linn, S.C., West, R.B., Pollack, J.R., Zhu, S., Hernandez-Boussard, T., Nielsen, T.O., Rubin, B.P., Patel, R., Goldblum, J.R., Siegmund, D., Botstein, D., Brown, P.O., Gilks, C.B., van de Rijn, M. Am. J. Pathol. (2003) [Pubmed]
  24. Isolation and characterization of human pituitary chorionic gonadotropin. Birken, S., Maydelman, Y., Gawinowicz, M.A., Pound, A., Liu, Y., Hartree, A.S. Endocrinology (1996) [Pubmed]
  25. Prediction of over-response to ovarian stimulation in an intrauterine insemination programme. Lashen, H., Afnan, M., McDougall, L., Clark, P. Hum. Reprod. (1999) [Pubmed]
  26. Leptin inhibits gonadotrophin-stimulated granulosa cell progesterone production by antagonizing insulin action. Brannian, J.D., Zhao, Y., McElroy, M. Hum. Reprod. (1999) [Pubmed]
  27. Corpus luteum response to exogenous HCG during the mid-luteal phase of the menstrual cycle. Tay, P.Y., Lenton, E.A. Clin. Endocrinol. (Oxf) (2000) [Pubmed]
  28. Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions. Kohlhammer, H., Schwaenen, C., Wessendorf, S., Holzmann, K., Kestler, H.A., Kienle, D., Barth, T.F., Möller, P., Ott, G., Kalla, J., Radlwimmer, B., Pscherer, A., Stilgenbauer, S., Döhner, H., Lichter, P., Bentz, M. Blood (2004) [Pubmed]
  29. Degenerate oligonucleotide primed-polymerase chain reaction-based array comparative genomic hybridization for extensive amplicon profiling of breast cancers : a new approach for the molecular analysis of paraffin-embedded cancer tissue. Daigo, Y., Chin, S.F., Gorringe, K.L., Bobrow, L.G., Ponder, B.A., Pharoah, P.D., Caldas, C. Am. J. Pathol. (2001) [Pubmed]
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