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Sample records for mullerian hoxa10 gene

  1. Regulation of CDX4 gene transcription by HoxA9, HoxA10, the Mll-Ell oncogene and Shp2 during leukemogenesis

    PubMed Central

    Bei, L; Shah, C; Wang, H; Huang, W; Platanias, L C; Eklund, E A

    2014-01-01

    Cdx and Hox proteins are homeodomain transcription factors that regulate hematopoiesis. Transcription of the HOX and CDX genes decreases during normal myelopoiesis, but is aberrantly sustained in leukemias with translocation or partial tandem duplication of the MLL1 gene. Cdx4 activates transcription of the HOXA9 and HOXA10 genes, and HoxA10 activates CDX4 transcription. The events that break this feedback loop, permitting a decreased Cdx4 expression during normal myelopoiesis, were previously undefined. In the current study, we find that HoxA9 represses CDX4 transcription in differentiating myeloid cells, antagonizing activation by HoxA10. We determine that tyrosine phosphorylation of HoxA10 impairs transcriptional activation of CDX4, but tyrosine phosphorylation of HoxA9 facilitates repression of this gene. As HoxA9 and HoxA10 are phosphorylated during myelopoiesis, this provides a mechanism for differentiation stage-specific Cdx4 expression. HoxA9 and HoxA10 are increased in cells expressing Mll-Ell, a leukemia-associated MLL1 fusion protein. We find that Mll-Ell induces a HoxA10-dependent increase in Cdx4 expression in myeloid progenitor cells. However, Cdx4 decreases in a HoxA9-dependent manner on exposure of Mll-Ell-expressing cells to differentiating cytokines. Leukemia-associated, constitutively active mutants of Shp2 block cytokine-induced tyrosine phosphorylation of HoxA9 and HoxA10. In comparison with myeloid progenitor cells that are expressing Mll-Ell alone, we find increased CDX4 transcription and Cdx4 expression in cells co-expressing Mll-Ell plus constitutively active Shp2. Increased Cdx4 expression is sustained on exposure of these cells to differentiating cytokines. Our results identify a mechanism for increased and sustained CDX4 transcription in leukemias co-overexpressing HoxA9 and HoxA10 in combination with constitutive activation of Shp2. This is clinically relevant, because MLL1 translocations and constitutive Shp2 activation co-exist in

  2. Mixed lineage leukaemia histone methylases 1 collaborate with ERα to regulate HOXA10 expression in AML

    PubMed Central

    Yao, Jie; Fang, Li-Chao; Yang, Zai-Lin; Huang, Hui; Li, Yan; Deng, Jun; Zheng, Junsong

    2014-01-01

    HOXA10, a homeobox-containing gene involved in definitive haematopoiesis, which implicated in the pathogenesis of AML (acute myeloid leukaemia), has been studied extensively. But the regulatory mechanism that drives HOXA10 expression is still unclear. In the present paper, HOXA10 regulated by MLL1 (mixed lineage leukaemia histone methylase 1) with an epigenetic way has been demonstrated. The HOXA10 promoter contains several EREs (oestrogen response elements), including ERE1 and ERE2, which are close to the transcription start site, and are associated with E2-mediated activation of HOXA10. It has been shown that knockdown of the ERα (oestrogen receptor α) suppresses E2-mediated activation of HOXA10. Similarly, knockdown of MLL1 suppresses activation of HOXA10 and is bound to the ERE of HOXA10 promoter in an E2-dependent manner by forming complex with ERα. Knockdown of ERα affects the E2-dependent binding of MLL1 into HOXA10 EREs, suggesting critical roles of ERα in recruiting MLL on the HOXA10 promoter. More interestingly, the methylation status of histone protein H3K4 (H3 at lysine 4) with E2 is much higher than without E2 treatment in leukaemia cell. On the contrary, the methylation status of HOXA10 promoter with E2 treatment is much lower, which elevate the HOXA10 expression. Moreover, with ERα knockdown, the H3K4 methylation level is also decrease in myeloid cell. Overall, it has been clearly demonstrated that HOXA10 is transcriptionally regulated by MLL1, which, in coordination with ERα, plays a critical role in this process with epigenetic way and suggests a potential anti-E2 treatment of AML. PMID:25307539

  3. [Expression of HoxA10 in acute leukemia and its significance].

    PubMed

    Huang, Ying; Li, Wei-Jia; Wei, Cai-Xia; Zhou, Zhi; Nie, Bo

    2005-12-01

    To investigate the expression of HoxA(10) mRNA in acute leukemia patients and its significance, HoxA(10) level was detected by reverse transcription polymerase chain reaction (RT-PCR) in 50 patients with acute leukemias, 7 healthy volunteers and 3 patients with ITP (idiopathic thrombocytopenic purpura). The regularity of the expression of HoxA(10) gene in acute leukemia and the relationship between HoxA(10) level and the prognosis of leukemia was explored. The results showed that HoxA(10) was expressed in all types of acute myelogenous leukemia; HoxA(10) message was also observed in acute lymphoblastic leukemia patients and part of control groups. 3 normal donors were found not to express HoxA(10). The level of HoxA(10) mRNA of acute myelogenous leukemia patients was significantly higher than that of acute lymphoblastic leukemia patients and controls (P < 0.01). HoxA(10) gene appeared to be more strongly expressed in AML-M(1) and -M(2) subtypes than in AML-M(4) and -M(5) subtypes, and the gene was notable high expressed in acute promyelocytic leukemia. The number of blast and promyeloid cells in the bone marrow was positive related with the level of HoxA (r = 0.635, P < 0.01). The level of HoxA(10) of 9 non-responsive patients was higher than that of 8 remission patients, but there was no significant difference between them (P = 0.258). HoxA(10) was overexpressed in acute myelogenous leukemia. It is concluded that HoxA(10) is a major transcription factor regulating hematopoiesis and a mark to differentiate lymphoid leukemia and myelogenous leukemia, but not a specific gene of cancer. The level of HoxA(10) is related with load of leukemic cells and curative effect, and can affect occurrence and development of leukemia in combination with many cytokines, HoxA(10) may facilitate the leukemia progression with another cofactors. PMID:16403259

  4. HOXA10 controls proliferation, migration and invasion in oral squamous cell carcinoma

    PubMed Central

    Carrera, Manoela; Bitu, Carolina C; de Oliveira, Carine Ervolino; Cervigne, Nilva K; Graner, Edgard; Manninen, Aki; Salo, Tuula; Coletta, Ricardo D

    2015-01-01

    Although HOX genes are best known for acting in the regulation of important events during embryogenesis, including proliferation, differentiation and migration, alterations in their expression patterns have been frequently described in cancers. In previous studies we analyzed the expression profile of the members of the HOX family of homeobox genes in oral samples of normal mucosa and squamous cell carcinoma (OSCC) and identified differently expressed genes such as HOXA10. The present study aimed to validate the increased expression of HOXA10 in OSCCs, and to investigate the effects arising from its knockdown in OSCC cells. The levels of HOXA10 mRNA were determined in human OSCC samples and cell lines by quantitative PCR, and HOXA10-mediated effects on proliferation, apoptosis, adhesion, epithelial-mesenchymal transition (EMT), migration and invasion were studied in HSC-3 tongue carcinoma cells by using retrovirus-mediated RNA interference. Higher expression of HOXA10 mRNA was observed in OSCC cell lines and in tumor tissues compared to normal controls. HOXA10 knockdown significantly reduced the proliferation of the tumor cells which was accompanied by increased levels of p21. HOXA10 silencing also significantly induced the expression of EMT markers and enhanced the adhesion, migration and invasion of HSC-3 cells. No effects on cell death were observed after HOXA10 knockdown. The results of the current study confirm the overexpression of HOXA10 in OSCCs, and further demonstrate that its expression is functionally associated with several important biological processes related to oral tumorigenesis, such as proliferation, migration and invasion. PMID:26097543

  5. Activation of matrix metalloproteinase-26 by HOXA10 promotes embryo adhesion in vitro.

    PubMed

    Jiang, Yue; Yan, Guijun; Zhang, Hui; Shan, Huizhi; Kong, Chengcai; Yan, Qiang; Xue, Bai; Diao, Zhenyu; Hu, Yali; Sun, Haixiang

    2014-03-14

    Successful embryonic implantation requires an effective maternal-embryonic molecular dialogue. However, the detailed mechanisms of epithelial-embryo adhesion remain poorly understood. Here, we report that matrix metalloproteinase-26 (MMP-26) is a novel downstream target gene of homeobox a 10 (HOXA10) in human endometrial cells. HOXA10 binds directly to a conserved TTAT unit (-442 to -439) located within the 5' regulatory region of the MMP-26 gene and regulates the expression and secretion of MMP-26 in a concentration-dependent manner. Moreover, the adenovirus-mediated overexpression of MMP-26 in Ishikawa cells markedly increased BeWo spheroid adhesion. An antibody blocking assay further demonstrated that the promotion of BeWo spheroid adhesion by HOXA10 and MMP-26 was significantly inhibited by pre-treatment with a specific antibody against MMP-26. These results demonstrate that the HOXA10-mediated expression of MMP-26 promotes embryo adhesion during the process of embryonic implantation. PMID:24565841

  6. Effect of intramural myomectomy on endometrial HOXA10 and HOXA11 mRNA expression at the time of implantation window

    PubMed Central

    Alizadeh, Zohreh; Faramarzi, Shamila; Saidijam, Massoud; Alizamir, Tahereh; Esna-Ashari, Farzaneh; Shabab, Nooshin; Farimani Sanoee, Marzieh

    2013-01-01

    Background: HOXA11 and HOXA10 are expressed in endometrium throughout the menstrual cycle and show a dramatic increase during the mid-luteal phase at the time of implantation. The expression of these genes is decreased in women with myomas. Objective: To determine whether myomectomy would reverse HOXA11 and HOXA10 expression, we evaluated the transcript levels of these genes in the endometria of patients before and after myomectomy. Materials and Methods: Expression of HOXA11 and HOXA10 were examined prospectively during the midluteal phase in endometrium obtained from infertile women (n=12) with myoma before and three months after myomectomy. Endometrial HOXA11 and HOXA10 expression were evaluated using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Endometrial HOXA11 and HOXA10 mRNAs expression levels (normalized to 18SrRNA) were increased insignificantly in endometrium of patients after myomectomy (p=0.7 and p=0.15 respectively). Conclusion: The results suggest that the alteration in expression pattern of these genes could not account for some aspects of fertility after myomectomy. This article extracted from M.Sc. thesis. (Shamila Faramarzi) PMID:24639724

  7. Traditional Chinese Medicine, the Zishen Yutai Pill, Ameliorates Precocious Endometrial Maturation Induced by Controlled Ovarian Hyperstimulation and Improves Uterine Receptivity via Upregulation of HOXA10

    PubMed Central

    Gao, Qi; Han, Lu; Li, Xiumei; Cai, Xia

    2015-01-01

    Controlled ovarian hyperstimulation (COH) is widely used in assisted reproductive technology (ART), but it often leads to precocious maturation of the endometrium such that it impairs embryonic implantation and limits pregnancy rates. Previous studies have shown the traditional Chinese medicine, the Zishen Yutai pill (ZYP), to be effective in treatment of threatened as well as recurrent miscarriages, and it can improve embryonic implantation rates in patients undergoing IVF treatment. In the present study, the ZYP has been found to ameliorate precocious endometrial maturation in a mouse model of different COH. Molecular evaluations, real-time PCR, relative RT-PCR, Western blotting, and immunohistochemistry have indicated that the ZYP increased the expression of HOXA10, an important marker of uterine receptivity. Elevation of HOXA10 led to further upregulation of its target gene, integrin β3, and downregulation of EMX2, two additional markers of uterine receptivity. In this way, the ZYP may mitigate COH-induced precocious maturation of the endometrium and improve uterine receptivity by upregulating HOXA10. PMID:25792996

  8. Increased Engraftment of Human Short Term Repopulating Hematopoietic Cells in NOD/SCID/IL2rγnull Mice by Lentiviral Expression of NUP98-HOXA10HD

    PubMed Central

    Zhao, Huifen; Humphries, Keith; Persons, Derek A.

    2016-01-01

    Techniques to expand human hematopoietic stem cells ex-vivo could be beneficial to the fields of clinical hematopoietic stem cell transplantation and gene therapy targeted at hematopoietic stem cells. NUP98-HOXA10HD is a relatively newly discovered fusion gene that in mouse transplant experiments has been shown to increase numbers of hematopoietic stem cells. We evaluated whether this fusion gene could be used to expand engrafting human primitive CD34+ cells in an immunodeficient mouse model. Gene transfer was achieved using a lentiviral based vector. The engraftment of mobilized peripheral blood human CD34+ cells grown in culture for one week after gene transfer was evaluated 3–4 months after transplant and found to be 2–3 fold higher in the NUP98-HOXA10HD groups as compared to controls. These data suggest an expansive effect at least at the short term human repopulating cell level. Further evaluation in long term repopulating models and investment in a NUP98-HOXA10HD protein seems worthy of consideration. Additionally, the results here provide strong impetus to utilize NUP98-HOXA10HD as a tool to search for underlying genes and pathways involved in hematopoietic stem cell expansion that can be enhanced and have an even more potent expansive effect. PMID:26761813

  9. Genetic variants in anti-Mullerian hormone and anti-Mullerian hormone receptor genes and breast cancer risk in Caucasians and African Americans.

    PubMed

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2014-01-01

    Anti-Mullerian hormone (AMH) regulates ovarian folliculogenesis by signaling via its receptors, and elevated serum AMH levels are associated with an increased risk of breast cancer. No previous studies have examined the effects of genetic variants in AMH-related genes on breast cancer risk. We evaluated the associations of 62 single nucleotide polymorphisms (SNPs) in AMH and its receptor genes, including AMH type 1 receptor (ACVR1) and AMH type 2 receptor (AMHR2), with the risk of breast cancer in the Women's Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 62 SNPs evaluated, two showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratios (ORs) (95% confidence interval (95% CI)) of those two SNPs (ACVR1 rs12694937[C] and ACVR1 rs2883605[T]) for the risk of breast cancer among Caucasian women were 2.33 (1.20-4.52) and 0.68 (0.47-0.98), respectively. The age-adjusted additive ORs (95% CI) of those two SNPs (ACVR1 rs1146031[G] and AMHR2 functional SNP rs2002555[G]) for the risk of breast cancer among African American women were 0.63 (0.44-0.92) and 1.67 (1.10-2.53), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in AMH-related genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:25379134

  10. Genetic variants in anti-Mullerian hormone and anti-Mullerian hormone receptor genes and breast cancer risk in Caucasians and African Americans

    PubMed Central

    Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R

    2014-01-01

    Anti-Mullerian hormone (AMH) regulates ovarian folliculogenesis by signaling via its receptors, and elevated serum AMH levels are associated with an increased risk of breast cancer. No previous studies have examined the effects of genetic variants in AMH-related genes on breast cancer risk. We evaluated the associations of 62 single nucleotide polymorphisms (SNPs) in AMH and its receptor genes, including AMH type 1 receptor (ACVR1) and AMH type 2 receptor (AMHR2), with the risk of breast cancer in the Women’s Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 62 SNPs evaluated, two showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratios (ORs) (95% confidence interval (95% CI)) of those two SNPs (ACVR1 rs12694937[C] and ACVR1 rs2883605[T]) for the risk of breast cancer among Caucasian women were 2.33 (1.20-4.52) and 0.68 (0.47-0.98), respectively. The age-adjusted additive ORs (95% CI) of those two SNPs (ACVR1 rs1146031[G] and AMHR2 functional SNP rs2002555[G]) for the risk of breast cancer among African American women were 0.63 (0.44-0.92) and 1.67 (1.10-2.53), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in AMH-related genes to the risk of developing breast cancer in either Caucasians or African Americans. PMID:25379134

  11. Knockdown of HOXA10 reverses the multidrug resistance of human chronic mylogenous leukemia K562/ADM cells by downregulating P-gp and MRP-1.

    PubMed

    Yi, Ying-Jie; Jia, Xiu-Hong; Wang, Jian-Yong; Li, You-Jie; Wang, Hong; Xie, Shu-Yang

    2016-05-01

    Multidrug resistance (MDR) of leukemia cells is a major obstacle in chemotherapeutic treatment. The high expression and constitutive activation of P-glycoprotein (P-gp) and multidrug resistance protein-1 (MRP-1) have been reported to play a vital role in enhancing cell resistance to anticancer drugs in many tumors. The present study aimed to investigate the reversal of MDR by silencing homeobox A10 (HOXA10) in adriamycin (ADR)-resistant human chronic myelogenous leukemia (CML) K562/ADM cells by modulating the expression of P-gp and MRP-1. K562/ADM cells were stably transfected with HOXA10-targeted short hairpin RNA (shRNA). The results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis showed that the mRNA and protein expression of HOXA10 was markedly suppressed following transfection with a shRNA-containing vector. The sensitivity of the K562/ADM cells to ADR was enhanced by the silencing of HOXA10, due to the increased intracellular accumulation of ADR. The accumulation of ADR induced by the silencing of HOXA10 may be due to the downregulation of P-gp and MRP-1. Western blot analysis revealed that downregulating HOXA10 inhibited the protein expression of P-gp and MRP-1. Taken together, these results suggest that knockdown of HOXA10 combats resistance and that HOXA10 is a potential target for resistant human CML. PMID:27035504

  12. Control of regional decidualization in implantation: Role of FoxM1 downstream of Hoxa10 and cyclin D3

    PubMed Central

    Gao, Fei; Bian, Fenghua; Ma, Xinghong; Kalinichenko, Vladimir V.; Das, Sanjoy K.

    2015-01-01

    Appropriate regulation of regional uterine stromal cell decidualization in implantation, at the mesometrial triangle and secondary decidual zone (SDZ) locations, is critical for successful pregnancy, although the regulatory mechanisms remain poorly understood. In this regard, the available animal models that would specifically allow mechanistic analysis of site-specific decidualization are strikingly limited. Our study found that heightened expression of FoxM1, a Forkhead box transcription factor, is regulated during decidualization, and its conditional deletion in mice reveals failure of implantation with regional decidualization defects such as a much smaller mesometrial decidua with enlarged SDZ. Analysis of cell cycle progression during decidualization both in vivo and in vitro demonstrates that the loss of FoxM1 elicits diploid cell deficiency with enhanced arrests prior to mitosis and concomitant upregulation of polyploidy. We further showed that Hoxa10 and cyclin D3, two decidual markers, control transcriptional regulation and intra-nuclear protein translocation of FoxM1 in polyploid cells, respectively. Overall, we suggest that proper regional decidualization and polyploidy development requires FoxM1 signaling downstream of Hoxa10 and cyclin D3. PMID:26350477

  13. Mullerian Duct Cyst Causing Bladder Outlet Obstruction in a Patient with HNF-1β Gene Deletion

    PubMed Central

    Honore, Matthew; Fowler, Ross; Kiosoglous, Anthony J.

    2016-01-01

    A 24-year-old male was referred to a tertiary hospital for a possible prostatic abscess. The patient went into acute urinary retention. Transurethral drainage was performed. MRI pelvis three days post-operatively identified the prostatic cystic structure as a müllerian duct cyst. Several other phenotypical features were noted on examination as well as findings on investigations. From these diagnosis of hepatocyte nuclear factor-1β (HNF-1β) gene deletion was made. PMID:27390584

  14. AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer

    PubMed Central

    Pépin, David; Sosulski, Amanda; Zhang, Lihua; Wang, Dan; Vathipadiekal, Vinod; Hendren, Katherine; Coletti, Caroline M.; Yu, Aaron; Castro, Cesar M.; Birrer, Michael J.; Gao, Guangping; Donahoe, Patricia K.

    2015-01-01

    To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines. Purified recombinant LRMIS protein successfully inhibited the growth of cancer spheroids in vitro in a panel of primary cell lines in four of six patients tested. Adeno-associated virus (AAV) -delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, AAV9 was used as a single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth of palpable tumors in patient-derived ovarian cancer xenografts from ascites (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood concentrations of MIS, which significantly inhibited the growth of three of five lethal chemoresistant serous adenocarcinoma PDXa models without signs of measurable or overt toxicity. Finally, we tested the frequency of MIS type II receptor expression in a tissue microarray of serous ovarian tumors by immunohistochemistry and found that 88% of patients bear tumors that express the receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides a potentially well-tolerated and effective treatment strategy poised for testing in patients with chemoresistant serous ovarian cancer. PMID:26216943

  15. AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer.

    PubMed

    Pépin, David; Sosulski, Amanda; Zhang, Lihua; Wang, Dan; Vathipadiekal, Vinod; Hendren, Katherine; Coletti, Caroline M; Yu, Aaron; Castro, Cesar M; Birrer, Michael J; Gao, Guangping; Donahoe, Patricia K

    2015-08-11

    To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines. Purified recombinant LRMIS protein successfully inhibited the growth of cancer spheroids in vitro in a panel of primary cell lines in four of six patients tested. Adeno-associated virus (AAV) -delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, AAV9 was used as a single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth of palpable tumors in patient-derived ovarian cancer xenografts from ascites (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood concentrations of MIS, which significantly inhibited the growth of three of five lethal chemoresistant serous adenocarcinoma PDXa models without signs of measurable or overt toxicity. Finally, we tested the frequency of MIS type II receptor expression in a tissue microarray of serous ovarian tumors by immunohistochemistry and found that 88% of patients bear tumors that express the receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides a potentially well-tolerated and effective treatment strategy poised for testing in patients with chemoresistant serous ovarian cancer. PMID:26216943

  16. The Role of Hox Genes in Female Reproductive Tract Development, Adult Function, and Fertility.

    PubMed

    Du, Hongling; Taylor, Hugh S

    2016-01-01

    HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Müllerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility. PMID:26552702

  17. Persistent Mullerian Duct Syndrome with Transverse Testicular Ectopia

    PubMed Central

    Kumar, P. Naresh; Venugopala, Kandgal

    2015-01-01

    Persistent Mullerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism characterized by the presence of Mullerian duct structures in a normal male with 46, XY karyotype. Transverse testicular ectopia (TTE) is rare form of testicular ectopia in which two testes are located on one inguinal side. The opposite scrotum is empty. PMDS with TTE is rare. We report a case of PMDS with TTE discovered during surgery for a right inguinal hernia in a 25-year-old male. PMID:27512542

  18. Serous Ovarian Carcinoma Recurring as Malignant Mixed Mullerian Tumor

    PubMed Central

    Hale, Demir; Senem, Demiroz Ahu; Ovgu, Aydin; Hakan, Erenel; Sennur, Ilvan; Zerrin, Calay; Fuat, Demirkiran

    2015-01-01

    Only five cases of recurrence of malignant mixed Mullerian tumor (carcinosarcoma) from the ovarian carcinoma have been published in the literature to our knowledge. A 64-year-old woman first underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy because of pelvic mass. Histological diagnosis was serous papillary carcinoma of the left ovary. After six courses of chemotherapy, CA125 level returned to normal range. However, she had persistent multiple mediastinal and para-aortic lymphadenopathies in spite of additional six courses of chemotherapy. Then she underwent the second operation about 2 years after primary surgery. Multiple excisional biopsies were taken from subcutaneous tissue, over the bowels and the left external iliac artery. The histopathological diagnosis which was confirmed by immunohistochemical study was malignant mixed Mullerian tumor for all metastatic foci. A rare case of ovarian serous papillary carcinoma recurring as malignant mixed Mullerian tumor is reported. PMID:26713165

  19. Persistent mullerian duct syndrome presenting as retractile testis with hypospadias: A rare entity

    PubMed Central

    Vanikar, Aruna V; Nigam, Lovelesh A; Patel, Rashmi D; Kanodia, Kamal V; Suthar, Kamlesh S; Thakkar, Umang G

    2016-01-01

    A rare entity of persistent mullerian duct syndrome usually presents with a common symptom of undescended testis (UDT) or hernia. Male pseudo-hermaphroditism with persistent internal mullerian duct structures can present with a 46, XY karyotype with normal external genitalia and. It arises due to deficiency of anti-mullerian substance, resulting from reduced production/responsiveness to mullerian duct, leading to persistence of mullerian duct along with normal development of Wolffian duct structures. Presence of mullerian structure prevents testicular descent increasing the risk of testicular vanishing syndrome. The authors here report a case of 16 years old phenotypical male who came with retractile right sided testis and left side UDT in the urology out-patient department. Explorative laparotomy was performed and an ill-defined mass was excised and sent for histopathological examination. Histopathology revealed presence of mullerian structures. The serum testosterone level was normal, buccal smear cytology and karyotyping revealed a 46, XY genotype of the patient. PMID:27326401

  20. Persistent mullerian duct syndrome presenting as retractile testis with hypospadias: A rare entity.

    PubMed

    Vanikar, Aruna V; Nigam, Lovelesh A; Patel, Rashmi D; Kanodia, Kamal V; Suthar, Kamlesh S; Thakkar, Umang G

    2016-06-16

    A rare entity of persistent mullerian duct syndrome usually presents with a common symptom of undescended testis (UDT) or hernia. Male pseudo-hermaphroditism with persistent internal mullerian duct structures can present with a 46, XY karyotype with normal external genitalia and. It arises due to deficiency of anti-mullerian substance, resulting from reduced production/responsiveness to mullerian duct, leading to persistence of mullerian duct along with normal development of Wolffian duct structures. Presence of mullerian structure prevents testicular descent increasing the risk of testicular vanishing syndrome. The authors here report a case of 16 years old phenotypical male who came with retractile right sided testis and left side UDT in the urology out-patient department. Explorative laparotomy was performed and an ill-defined mass was excised and sent for histopathological examination. Histopathology revealed presence of mullerian structures. The serum testosterone level was normal, buccal smear cytology and karyotyping revealed a 46, XY genotype of the patient. PMID:27326401

  1. A rare case of Turner's syndrome presenting with Mullerian agenesis.

    PubMed

    Vaddadi, Suresh; Murthy, Ramana S V; Rahul, C H; Kumar, Vinod L

    2013-10-01

    Turner's syndrome also called as Ullrich Turner's syndrome, is a disease of unclear pathogenesis characterized by complete or partial absence of one sex chromosome, with or without cell line mosaicism in a phenotypic female with short stature. Various anomalies result in a constellation of features, of which the most disturbing is primary amenorrhea due to gonadal dysgenesis. Hormone therapy in these patients can often result in successful menstruation, and scope for subsequent pregnancy because of anatomically normal uterus and vagina. Coexisting Mullerian agenesis in these patients can jeopardize the chances of future pregnancy as they have associated structural abnormalities of the uterus and vagina. We report a rare case of middle-aged female with Turner's syndrome and Mullerian agenesis having absent secondary sexual characters and missing uterus with incompletely formed vagina. PMID:24672170

  2. Persistent Mullerian Duct Syndrome with Ovarian Endometriosis-A Rare Case Report

    PubMed Central

    Hippargi, Surekha B.; Mestri, Namrata B.; Mehrotra, Nikhil M.

    2016-01-01

    Persistent Mullerian Duct Syndrome (PMDS) is a rare form of internal male pseudohermaphroditism, characterised by presence of Mullerian duct derivatives in a genotypic and phenotypic male. It is caused by absence of anti- Mullerian hormone or defective functioning of its receptors. We report a case of 19-year-old cryptorchid male with history of orchideopexy who was clinically and radiologically diagnosed as left sided chylocele. A definitive diagnosis of PMDS with ovarian endometriosis was made on histopathological examination which is important for genetic counselling and to reduce complications like infertility and neoplastic transformation. We report this case of PMDS with ovary showing evidence of endometriosis for its rarity. PMID:27042476

  3. [A case of Mullerian duct cyst torsion combined with bladder cancer].

    PubMed

    Zhu, Fangpei; Ren, Qingling

    2016-06-28

    The diagnosis and treatment of a patient with Mullerian duct cyst torsion combined with bladder cancer were retrospectively analyzed. The patient received an open abdominal operation with right accessory resection plus pelvic adhesion release, and conducted microscopic examination for the bladder under general anesthesia. The results of histopathological examination confirmed the diagnosis of Mullerian duct cyst and papillary urothelial carcinoma at low level. After surgery, the patient received chemotherapy and follow-up observation, and all the indices for the patient were normal and no obvious discomfort. Although the final diagnosis of Mullerian duct cysts is based on histopathological examination, ultrasonography, CT scan and MRI can also detect it. Most of the Mullerian duct cysts are benign, and surgical excision is safe and effective. PMID:27374452

  4. Anti-mullerian hormon level and polycystic ovarian syndrome diagnosis

    PubMed Central

    Zadehmodarres, Shahrzad; Heidar, Zahra; Razzaghi, Zahra; Ebrahimi, Leili; Soltanzadeh, Kaveh; Abed, Farhang

    2015-01-01

    Background: Polycystic ovarian syndrome (PCOS) is a common endocrinopathy that accompanied with long term complications. The early diagnosis of this syndrome can prevent it. Objective: The aim was to determine the role of anti-mullerian hormon (AMH) in PCOS diagnosis and to find cut off level of it. Materials and Methods: In this cross sectional study, 117 women between 20-40 years old were participated in two groups: 60 PCOS women (based on Rotterdam criteria consensus) as the case group and 57 normal ovulatory women as the control group. In day 2-4 of cycle, transvaginal sonography was performed and serum hormonal level of AMH, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone, fasting blood sugar (FBS), thyroid stimulating hormone (TSH), and prolactin (PRL) were measured in all of participants. For all of them score of hirsutism (base on Freeman-Galloway scoring) was determined. Results: There were statistically significant in irregular pattern of menstruation, AMH and FSH level, and presence of hirsutism between two groups. But regarding mean of age, body mass index, plasma level of PRL, TSH, LH, Testosterone, FBS, and E2 differences were not significant. Construction by ROC curve present 3.15 ng/ml as AMH cut off with 70.37% sensitivity and 77.36% specificity in order to PCOS diagnosis. Conclusion: AMH with cut off level of 3.15 ng/ml with sensitivity 70.37% and specificity 77.36% could use for early diagnosis of PCOS patients. PMID:26131012

  5. Development of an efficiently cleaved, bioactive, highly pure FLAG-tagged recombinant human Mullerian Inhibiting Substance

    PubMed Central

    Papakostas, Thanos D.; Pieretti-Vanmarcke, Rafael; Nicolaou, Fotini; Thanos, Aristomenis; Trichonas, George; Koufomichali, Xanthi; Anago, Kosisochukwu; Donahoe, Patricia K.; Teixeira, Jose; MacLaughlin, David T.; Vavvas, Demetrios

    2013-01-01

    Mullerian Inhibiting Substance (MIS), a member of the TGF-β family, causes regression of the Mullerian duct in male embryos, after binding to Mullerian Inhibiting Substance Receptor II (MISRII). It has also been extensively demonstrated that it can inhibit proliferation of various cancer cell lines such as ovarian, prostate, and breast cancer in vitro and in vivo. Hence, the availability of a recombinant, epitope tagged, bioactive MIS is important for the selection of patients for treatment and for probing novel molecular targets for MIS in various tissues. To this end, we have expressed a recombinant, internally FLAG-tagged form of hMIS with the tag (DYKDDDDK) immediately after the cleavage site (427–428) of MIS at the C-terminus with a modified dibasic cleavage motif sequence. We show that this construct results in a highly pure, endogenously processed (cleaved) FLAG MIS, that causes complete regression of the Mullerian Duct in an organ culture assay. In addition, purified FLAG MIS was able to bind and affinity purify both transfected and endogenous MIS type II receptor. The availability of this fully functional, epitope tagged form of MIS should facilitate scale-up for preclinical and clinical use and should also be used for the study of MIS binding proteins and for tracking in pharmacokinetic studies. PMID:19755162

  6. CHANGES IN PLASMA MULLERIAN INHIBITING SUBSTANCE AND BRAIN-DERIVED NEUROTROPHIC FACTOR AFTER CHEMOTHERAPY IN PREMENOPAUSAL WOMEN

    PubMed Central

    Aslam, Muhammad Faisal; Merhi, Zaher O; Ahmed, Safaa; Kuzbari, Oumar; Seifer, David B.; Minkoff, Howard

    2010-01-01

    Eight premenopausal women with cancer had blood drawn for brain-derived neurotrophic factor (BDNF) and Mullerian Inhibiting Substance (MIS) before and three months after receiving chemotherapy. Unlike MIS, BDNF levels were not reduced following chemotherapy. PMID:21075370

  7. A Rare Case Report of Inguinal Hernia with Persistent Mullerian Duct and Klinefelter Syndrome

    PubMed Central

    Om, Prabha; Shridatt, Sharma Ankit; Patni, Ankur; Verma, Naveen

    2016-01-01

    Inguinal hernia in male is a common problem but having female reproductive organs in hernial sac is rare. It occur because of failure of mullerian duct to regress in a male fetus during embryonic development, result in a syndrome known as Persistent Mullerian Duct Syndrome (PMDS), which is a rare entity of male pseudohermaphroditism. We hereby present a case of 21-year-old male patient reported with complains of cryptorchidism and inguinal hernia. Generally diagnosis of PMDS was established during investigation like ultrasonography, MRI for localization of undescended testis and during surgical exploration for inguinal hernia or cryptorchidism. Our patient was operated by bilateral inguinal incision; hernial sac contained adult size uterus fallopian tube and upper 2/3rd of vagina. On karyotyping it was found that he was a case of klinefelter syndrome also. Association of PMDS with klinefelter syndrome is very rare. PMID:27504355

  8. A Rare Case Report of Inguinal Hernia with Persistent Mullerian Duct and Klinefelter Syndrome.

    PubMed

    Dadheech, Darpan; Om, Prabha; Shridatt, Sharma Ankit; Patni, Ankur; Verma, Naveen

    2016-06-01

    Inguinal hernia in male is a common problem but having female reproductive organs in hernial sac is rare. It occur because of failure of mullerian duct to regress in a male fetus during embryonic development, result in a syndrome known as Persistent Mullerian Duct Syndrome (PMDS), which is a rare entity of male pseudohermaphroditism. We hereby present a case of 21-year-old male patient reported with complains of cryptorchidism and inguinal hernia. Generally diagnosis of PMDS was established during investigation like ultrasonography, MRI for localization of undescended testis and during surgical exploration for inguinal hernia or cryptorchidism. Our patient was operated by bilateral inguinal incision; hernial sac contained adult size uterus fallopian tube and upper 2/3(rd) of vagina. On karyotyping it was found that he was a case of klinefelter syndrome also. Association of PMDS with klinefelter syndrome is very rare. PMID:27504355

  9. Persistent Mullerian Duct Syndrome with Embryonal Cell Carcinoma along with Ectopic Cross Fused Kidney

    PubMed Central

    Bharath, NR Manju; Narayana, V; Raja, V Om Pramod Kumar; Jambula, Pranav Reddy

    2016-01-01

    Persistent Mullerian Duct Syndrome (PMDS) is a form of internal male pseudohermaphroditism, where there is normal development of male secondary sexual characters, along with the presence of bilateral fallopian tubes and uterus. Majority of these cases go undetected and some cases are accidentally diagnosed while investigating for other problems. Cross fused renal ectopia is a condition where one kidney lies in the opposite side, fused to the other kidney. We present an extremely rare case of a phenotypical male presenting with mass per abdomen and bilateral cryptorchidism, turned out to have uterus with bilateral fallopian tubes, ectopic cross fused right kidney and Embryonal cell carcinoma of left undescended testis. PMID:26894123

  10. Measurement of anti-Mullerian hormone: performances of a new ultrasensitive immunoassay.

    PubMed

    Gruson, Damien; Homsak, Evgenija

    2015-04-01

    The measurement of anti-Mullerian hormone (AMH) is relevant for the evaluation of primary ovarian insufficiency, success of assisted reproductive therapies, and also to support the diagnosis of polycystic ovary syndrome. Our study demonstrated excellent analytical performances for the Ansh Laboratories AMH immunoassay and an overall good agreement with the AMH Gen II assay. Nevertheless, the two AMH immunoassays are not using the same couple of antibodies and therefore not commutable and the definition of specific reference values and cut-point remains necessary. PMID:25575745

  11. Prolonged Survival of a Patient With Pelvic Recurrence of Ovarian Malignant Mixed Mullerian Tumor After Chemoradiotherapy

    PubMed Central

    Homaei Shandiz, Fatemeh; Kadkhodayan, Sima; Hsanzade Mofrad, Malihe; Yousefi Roodsari, Zohre; Sharifi Sistani, Noorieh; Nabizadeh Marvast, Majid; Sadeghei, Mahbobe

    2014-01-01

    Introduction: Malignant Mixed Mullerian Tumor (MMMT) is a very rare tumor, accounting for less than 1% of all ovarian cancers. Case Presentation: We present a 64-year-old woman with stage III MMMT of ovary that was treated with platinum-based chemotherapy after optimal cytoreductive surgery. After 25 months of being disease free, she had a pelvic recurrence and a good response to chemoradiotherapy. Conclusions: Optimal cytoreductive surgery and chemotherapy may be the best treatment in MMMT but more discussion and experiences are needed regarding the effectiveness of radiotherapy. PMID:25593719

  12. Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107.

    PubMed

    Barbie, Thanh U; Barbie, David A; MacLaughlin, David T; Maheswaran, Shyamala; Donahoe, Patricia K

    2003-12-23

    In addition to causing regression of the Mullerian duct in the male embryo, Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian cancer cells, which are known to be of Mullerian origin. Because the uterine cervix is derived from the same Mullerian duct precursor as the epithelium of the ovary, we tested the hypothesis that cervical cancer cells might also respond to MIS. A number of cervical cancer cell lines express the MIS type II receptor, and MIS inhibits the growth of both human papilloma virus-transformed and non-human papilloma virus-transformed cervical cell lines, with a more dramatic effect seen in the latter. As in the ovarian cancer cell line OVCAR8, suppression of growth of the C33A cervical cancer cell line by MIS is associated with induction of the p16 tumor suppressor protein. However, in contrast to OVCAR8 cells, induction of p130 and p107 appears to play an important role in the inhibition of growth of C33A cells by MIS. Finally, normal cervical tissue expresses the MIS type II receptor in vivo, supporting the idea that MIS could be a targeted therapy for cervical cancer. PMID:14671316

  13. Secretory and basal cells of the epithelium of the tubular glands in the male Mullerian gland of the caecilian Uraeotyphlus narayani (Amphibia: Gymnophiona).

    PubMed

    George, Jancy M; Smita, Matthew; Kadalmani, Balamuthu; Girija, Ramankutty; Oommen, Oommen V; Akbarsha, Mohammad A

    2004-12-01

    Caecilians are exceptional among the vertebrates in that males retain the Mullerian duct as a functional glandular structure. The Mullerian gland on each side is formed from a large number of tubular glands connecting to a central duct, which either connects to the urogenital duct or opens directly into the cloaca. The Mullerian gland is believed to secrete a substance to be added to the sperm during ejaculation. Thus, the Mullerian gland could function as a male accessory reproductive gland. Recently, we described the male Mullerian gland of Uraeotyphlus narayani using light and transmission electron microscopy (TEM) and histochemistry. The present TEM study reports that the secretory cells of both the tubular and basal portions of the tubular glands of the male Mullerian gland of this caecilian produce secretion granules in the same manner as do other glandular epithelial cells. The secretion granules are released in the form of structured granules into the lumen of the tubular glands, and such granules are traceable to the lumen of the central duct of the Mullerian gland. This is comparable to the situation prevailing in the epididymal epithelium of several reptiles. In the secretory cells of the basal portion of the tubular glands, mitochondria are intimately associated with fabrication of the secretion granules. The structural and functional organization of the epithelium of the basal portion of the tubular glands is complicated by the presence of basal cells. This study suggests the origin of the basal cells from peritubular tissue leukocytes. The study also indicates a role for the basal cells in acquiring secretion granules from the neighboring secretory cells and processing them into lipofuscin material in the context of regression of the Mullerian gland during the period of reproductive quiescence. In these respects the basal cells match those in the epithelial lining of the epididymis of amniotes. PMID:15487004

  14. Expression and regulation of anti-mullerian hormone in an oviparous species, the hen.

    PubMed

    Johnson, P A; Kent, T R; Urick, M E; Giles, J R

    2008-01-01

    Anti-mullerian hormone (AMH) has a critical role in regression of the mullerian duct system during development in male mammalian and avian species and in regression of the right oviduct in female avian species. AMH in adult female birds has not been investigated. Chicken-specific cDNA primers were used to isolate Amh by RT-PCR. This probe was used in Northern blot analysis to identify a 2.8-kb band with expression in total ovarian RNA and in granulosa cell RNA. Quantitative real-time PCR was used to assess Amh expression in follicles of different maturity (1, 3, 5, and 6-12 mm and the largest F1 follicle; n = 4-6 of each size). There was an increased amount of Amh mRNA in the granulosa layer of the smaller follicles and a lower amount in the granulosa layer of the larger follicles (P < 0.01). There was no difference in granulosa Amh expression between the germinal disc and non-germinal disc region of 6- to 12-mm follicles, although expression differed with follicle size (P < 0.01). To examine hormone regulation of Amh, granulosa cells (from 6- to 8-mm follicles) were cultured with various concentrations of estradiol (E(2)) and progesterone (P(4)), and Amh mRNA was assessed. Neither E(2) nor P(4) influenced Amh mRNA accumulation. Granulosa cells were also cultured in the presence of oocyte-conditioned medium (OCM), which decreased Amh mRNA expression in a dose-related manner (P < 0.05); FSH receptor expression was not affected. Heat treatment of OCM abolished the effect, but growth differentiation factor 9 antiserum did not block the suppression. Immunohistochemistry confirmed that the granulosa layer was the predominant source of AMH in the small follicles of the hen and indicated that AMH was present early in follicle development, with expression in very small follicles (approximately 150 mum). PMID:17881771

  15. A patient with Mullerian abnormalities, renal dysplasia, cervical spine fusion, cataracts and intellectual disability: MURCS-plus?

    PubMed

    Tan, Tiong Yang; Whitelaw, Charlotte; Savarirayan, Ravi

    2007-10-01

    We report a 15-year-old girl with features of the MURCS (Mullerian abnormalities, renal agenesis/ectopy and cervicothoracic somite dysplasia) association and birth defects not typically associated with MURCS. In addition to seizures and intellectual disability, she has cortical brain heterotopia, bilateral subclinical cataracts, submucous cleft palate and patent ductus arteriosus. We propose that this patient represents a more severe form of MURCS, or 'MURCS-plus', which may represent a defect of or insult to mesodermal morphogenesis. PMID:17786121

  16. Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells

    PubMed Central

    Zhang, Shiwu; Mercado-Uribe, Imelda; Sood, Anil; Bast, Robert C.; Liu, Jinsong

    2016-01-01

    Stromal cells are generally considered to be derived primarily from the host's normal mesenchymal stromal cells or bone marrow. However, the origins of stromal cells have been quite controversial. To determine the role of polyploidy in tumor development, we examined the fate of normal mullerian epithelial cells during the immortalization and transformation process by tracing the expression of SV40 large T antigen. Here we show that immortalized or HRAS-transformed mullerian epithelial cells contain a subpopulation of polyploid giant cells that grow as multicellular spheroids expressing hematopoietic markers in response to treatment with CoCl2. The immortalized or transformed epithelial cells can transdifferentiate into stromal cells when transplanted into nude mice. Immunofluorescent staining revealed expression of stem cell factors OCT4, Nanog, and SOX-2 in spheroid, whereas expression of embryonic stem cell marker SSEA1 was increased in HRAS-transformed cells compared with their immortalized isogenic counterparts. These results suggest that normal mullerian epithelial cells are intrinsically highly plastic, via the formation of polyploid giant cells and activation of embryonic stem-like program, which work together to promote the coevolution of neoplastic epithelial cells and multiple lineage stromal cells. PMID:27382431

  17. Zebrafish Hoxa and Evx-2 genes: cloning, developmental expression and implications for the functional evolution of posterior Hox genes.

    PubMed

    Sordino, P; Duboule, D; Kondo, T

    1996-10-01

    Vertebrate Hox genes are required for the establishment of regional identities along body axes. This gene family is strongly conserved among vertebrates, even in bony fish which display less complex ranges of axial morphologies. We have analysed the structural organization and expression of Abd-B related zebrafish HoxA cluster genes (Hoxa-9, Hoxa-10, Hoxa-11 and Hoxa-13) as well as of Evx-2, a gene closely linked to the HoxD complex. We show that the genomic organization of Hoxa genes in fish resembles that of tetrapods albeit intergenic distances are shorter. During development of the fish trunk, Hoxa genes are coordinately expressed, whereas in pectoral fins, they display transcript domains similar to those observed in developing tetrapod limbs. Likewise, the Evx-2 gene seems to respond to both Hox- and Evx-types of regulation. During fin development, this latter gene is expressed as the neighbouring Hox genes, in contrast to its expression in the central nervous system which does not comply with colinearity and extends up to anterior parts of the brain. These results are discussed in the context of the functional evolution of Hoxa versus Hoxd genes and their different roles in building up paired appendages. PMID:8951794

  18. Assay Reproducibility and Within-Person Variation of Mullerian Inhibiting Substance

    PubMed Central

    Dorgan, Joanne F.; Spittle, Cynthia S.; Egleston, Brian L.; Shaw, Christiana M.; Kahle, L. L.; Brinton, Louise A.

    2009-01-01

    Objectives To assess reproducibility of a commercial mullerian inhibiting substance (MIS) assay and evaluate within-person variation in serum MIS levels. Design Assay reproducibility was evaluated by measuring MIS in multiple serum aliquots from the same blood collection. Within-person variation was assessed by measuring MIS in serum collected twice from the same individuals. Setting Fox Chase Cancer Center, Philadelphia, PA Patient(s) Assay reproducibility was evaluated using serum from 5 volunteers with regular menstrual cycles. Within-person variation was evaluated in serum from 20 premenopausal women who donated blood twice at least 1 year apart. Intervention(s) For both studies, samples were randomly ordered in batches and laboratory personnel were blinded to which aliquots were from the same subject. Main Outcome Measure(s) MIS was measured using an enzyme-linked immunosorbent assay. Results Within- and between-batch coefficients of variation (CVs) of the assay were 7.9% and 12.3%, respectively. After deleting one subject with extreme values, these CVs decreased to 7.6% and 7.7%, respectively. Within- and between-subject variance in MIS measurements were 2.19 and 0.31, respectively, and the intraclass correlation coefficient was .88 (95% confidence interval = .77 – .98). Conclusion(s) MIS serum concentration is relatively stable over one year in premenopausal women and can be measured with good reproducibility using a commercial kit. PMID:19409547

  19. Primary Ovarian Malignant Mixed Mullerian Tumour: A Case Report and Brief Review of Literature

    PubMed Central

    Çakir, Tansel; Ilhan, Tolgay Tuyan; Karabagli, Pinar; Çelik, Çetin

    2016-01-01

    Malignant Mixed Mullerian Tumour of the Ovary (OMMMT), also referred to as carcinosarcoma is a very rare tumour accounting for less than 1% of all ovarian cancers. Due to the rarity of OMMMT, little is known about the disease course and outcome of women with these tumours. It is important to evaluate because of its aggressive behaviour with extremely unfavourable prognosis. These tumours are composed of both malignant epithelial and mesenchymal elements. Current data in the literature is still limited to small case series and case reports, therefore, its optimal treatment is somewhat controversial. In the current report, we introduce a case of OMMMT which was successfully treated with Platinum-based combination chemotherapy after optimal cytoreductive surgery. The clinical manifestations, pathologic characteristics, diagnosis and management of these tumours are reviewed here. Although the most effective treatment is currently unknown, optimal cytoreductive surgery and platinum-based chemotherapy appears to improve the outcomes. Despite the aggressive nature of this tumour and its poor response to the treatment, management works best when cancer is found early. The stage of the disease is the most important prognostic factor. Therefore, the crucial question is how to diagnose the cancer at earlier stages rather than seeking the optimal treatment. PMID:27134951

  20. Anti-Mullerian Hormone: Above and Beyond Conventional Ovarian Reserve Markers

    PubMed Central

    Jamil, Zehra; Fatima, Syeda Sadia; Ahmed, Khalid; Malik, Rabia

    2016-01-01

    Management of ovarian dysfunctions requires accurate estimation of ovarian reserve (OR). Therefore, reproductive hormones and antral follicle count (AFC) are assessed to indicate OR. Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show OR decline. In this review we discuss the dynamics of circulating AMH that remarkably vary with sex and age. As it emerges as a marker of gonadal development and reproductive disorders, here we summarize the role of AMH in female reproductive physiology and provide evidence of higher accuracy in predicting ovarian response to stimulation. Further, we attempt to compile potential clinical applications in children and adults. We propose that AMH evaluation has a potential role in effectively monitoring chemotherapy and pelvic radiation induced ovarian toxicity. Furthermore, AMH guided ovarian stimulation can lead to individualization of therapeutic strategies for infertility treatment. However future research on AMH levels within follicular fluid may pave the way to establish it as a marker of “quality” besides “quantity” of the growing follicles. PMID:26977116

  1. Comparative analysis of P16 and P53 expression in uterine malignant mixed mullerian tumors.

    PubMed

    Buza, Natalia; Tavassoli, Fattaneh A

    2009-11-01

    Recent studies have shown that, in addition to cervical carcinomas, a substantial proportion of endometrial adenocarcinomas are also immunoreactive with p16. The expression of p16 in uterine malignant mixed mullerian tumors (MMMTs), in contrast, has not yet been analyzed in a large series. To our knowledge, we present the first study assessing p16 expression in both components of MMMTs. We performed p16 and p53 immunostains on 30 cases of uterine MMMTs. Both the epithelial and mesenchymal components were subclassified; p16 and p53 immunoreactions were assessed using a semiquantitative scoring system. p16 overexpression was noted in the carcinomatous component in 96.7% (29/30), and in the sarcomatous component in 86.7% (26/30) of cases. In comparison, p53 immunoreactivity was present in the carcinomatous component in 76.7% (23/30), and in the sarcomatous component in 83.3% (25/30) of cases. p16 immunoreactivity was more intense and diffuse than p53 in 40% of type I, 30% of type II carcinomas, and 27% of sarcomatous components. There was no significant difference in p16 or p53 immunoreactivity between the homologous and heterologous sarcomas. The concordance rates for p16 and p53 immunoreactivity between the 2 components were 83% and 90%, respectively. We conclude that p16 immunostain is positive in the vast majority of uterine MMMTs with no significant difference in staining between the 2 components. Compared with p53, p16 immunoreactivity is significantly more intense and diffuse in both components. Our findings indicate that alterations in the p16-Rb pathway play an important role in the pathogenesis of uterine MMMTs. PMID:19851197

  2. Epigenetic control of fetal bone development through HoxA10 in the rat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological studies show that quality of nutrition during intrauterine and early postnatal life impact the risk of low bone mass and fracture later in life. Maternal consumption of high-fat diets has been demonstrated to affect health outcomes, such as: brain development; obesity; insulin resist...

  3. Contribution of the secretory material of caecilian (amphibia: Gymnophiona) male Mullerian gland to motility of sperm: a study in Uraeotyphlus narayani.

    PubMed

    George, Jancy M; Smita, Mathew; Kadalmani, Balamuthu; Girija, Ramankutty; Oommen, Oommen V; Akbarsha, Mohammad A

    2005-02-01

    Caecilians are a unique group of limbless burrowing amphibians with discontinuous distribution. Several caecilian species are viviparous, and all practice internal fertilization. In amniotic vertebrates the sperm undergo post-testicular physiological maturation when they are initiated into motility under the influence of an epididymal secretion. Further, during ejaculation mammalian sperm are suspended in a fluid secreted by the male accessory sex glands, viz., prostate gland and seminal vesicles. Caecilians lack comparable glands, but still practice internal fertilization. Uniquely, male caecilians retain the Mullerian ducts in the adults as a pair of functional glands. It has long been hypothesized, based on indirect evidence, that the Mullerian gland would be a male accessory sex gland, secreting a fluid in which sperm are suspended during ejaculation and which would also provide nutritional support to the ejaculated sperm. In the present study, the secretory material of the Mullerian gland of Uraeotyphlus narayani was mixed with sperm obtained from the testis, and the changes in motility were recorded. Uraeotyphlus narayani sperm possess a perforatorium of the acrosome proceeding deep into the endonuclear canal of the nucleus. The midpiece is characterized by closely applied centrioles, the anterior ends of the axoneme and axial fiber, and a mitochondrial sheath. The long tail has an undulating membrane on one side, supported by the axoneme and an axial fiber. The live sperm possess a mitochondrial vesicle, also known as the cytoplasmic droplet, anywhere along the head and the midpiece, as in anuran sperm, which is shed from sperm that have ceased motility. Uraeotyphlus narayani sperm are motile the moment they are released directly from the testis, indicating that the sperm do not require post-testicular physiological maturation. On being mixed with the secretory material of the Mullerian gland, the spermatozoa are enhanced in speed as well as duration of

  4. Impact of breast cancer on anti-mullerian hormone levels in young women.

    PubMed

    Su, H I; Flatt, S W; Natarajan, L; DeMichele, A; Steiner, A Z

    2013-01-01

    Young women with breast cancer face treatments that impair ovarian function, but it is not known if malignancy itself impacts ovarian reserve. As more breast cancer patients consider future fertility, it is important to determine if ovarian reserve is impacted by cancer, prior to any therapeutic intervention. A cross-sectional study was conducted comparing if ovarian reserve, as measured by anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), and inhibin B (inhB), differed between 108 women with newly diagnosed breast cancer and 99 healthy women without breast cancer. Breast cancer participants were ages 28-44 and were recruited from two clinical breast programs. Healthy women ages 30-44 without a history of infertility were recruited from gynecology clinics and the community. The median age (interquartile range) was 40.2(5.5) years for breast cancer participants and 33.0(4.6) years for healthy controls. The unadjusted geometric mean AMH levels (SD) for breast cancer participants and controls were 0.66(3.6) and 1.1(2.9) ng/mL, respectively. Adjusting for age, body mass index, gravidity, race, menstrual pattern, and smoking, mean AMH levels were not significantly different between breast cancer participants and healthy controls (0.85 vs. 0.76 ng/mL, p = 0.60). FSH and inhB levels did not differ by breast cancer status. In exploratory analysis, the association between AMH and breast cancer status differed by age (p-interaction = 0.02). AMH may be lower with breast cancer status in women older than 37. In younger women, AMH levels did not differ significantly by breast cancer status. Among the youngest of breast cancer patients, ovarian reserve as measured by AMH, FSH, and inhibin B did not differ significantly from healthy women of similar age. In older breast cancer patients, ovarian reserve may be adversely impacted by cancer status. These findings support the potential success and need for fertility preservation strategies prior to institution of

  5. The Anti Mullerian Hormone- A Novel Marker for Assessing the Ovarian Reserve in Women with Regular Menstrual Cycles

    PubMed Central

    Kalaiselvi, V. S; P, Saikumar; K, Prabhu; Krishna G, Prashanth

    2012-01-01

    Background Ovarian Reserve (OR) is a term which describes the functional potential of the ovary, which constitutes the size of the ovarian follicle pool and reflects the number and quality of the oocytes which are within it. Assessment of the OR helps in reflecting the reproductive potential of women. Various markers are available for assessing the OR and the best marker is the Anti Mullerian Hormone (AMH) which reflects the ovarian follicular pool in the ovary. In this study, the serum level of AMH/MIS(Mullerian Inhibiting Substance)was estimated to assess the ovarian reserve in both fertile and infertile women. Objective To assess the ovarian reserve in women of the fertile and subfertile groups with regular cycles, who were in the age range of 26 -33yrs, by estimating the level of AMH and those of other hormones like FSH and E2 and also to calculate the ovarian volume and the Antral follicular count by an ultrasonographic method. Materials and Methods Thirty fertile and thirty sub fertile women whose ages ranged from 26-33yrs were included as group 1 and group 2 respectively. The hormones like AMH ,FSH and oestradiol were assayed. Measurement of the ovarian volume and the antral follicular count by doing a transvaginal ultrasonogram, was done in all the subjects who were involved in both the groups. The correlation test was studied between the variables and the test of significance of the variables between the 2 groups was also analyzed by the Statistical Package Of Social Sciences (SPSS). Results The Antral Follicular Count (AFC) and the ovarian volume were negatively correlated with the age. The ovarian volume was positively correlated with the AFC. The FSH negatively correlated with the AFC. The Anti Mullerian Hormone negatively correlated with the age, and it positively correlated with the AFC. The mean values of AFC, FSH, and AMH were also statistically significant between the two groups. Conclusion AMH can be considered as a marker for assessing the

  6. Gene identification for risk of relapse in stage I lung adenocarcinoma patients: a combined methodology of gene expression profiling and computational gene network analysis.

    PubMed

    Ludovini, Vienna; Bianconi, Fortunato; Siggillino, Annamaria; Piobbico, Danilo; Vannucci, Jacopo; Metro, Giulio; Chiari, Rita; Bellezza, Guido; Puma, Francesco; Della Fazia, Maria Agnese; Servillo, Giuseppe; Crinò, Lucio

    2016-05-24

    Risk assessment and treatment choice remains a challenge in early non-small-cell lung cancer (NSCLC). The aim of this study was to identify novel genes involved in the risk of early relapse (ER) compared to no relapse (NR) in resected lung adenocarcinoma (AD) patients using a combination of high throughput technology and computational analysis. We identified 18 patients (n.13 NR and n.5 ER) with stage I AD. Frozen samples of patients in ER, NR and corresponding normal lung (NL) were subjected to Microarray technology and quantitative-PCR (Q-PCR). A gene network computational analysis was performed to select predictive genes. An independent set of 79 ADs stage I samples was used to validate selected genes by Q-PCR.From microarray analysis we selected 50 genes, using the fold change ratio of ER versus NR. They were validated both in pool and individually in patient samples (ER and NR) by Q-PCR. Fourteen increased and 25 decreased genes showed a concordance between two methods. They were used to perform a computational gene network analysis that identified 4 increased (HOXA10, CLCA2, AKR1B10, FABP3) and 6 decreased (SCGB1A1, PGC, TFF1, PSCA, SPRR1B and PRSS1) genes. Moreover, in an independent dataset of ADs samples, we showed that both high FABP3 expression and low SCGB1A1 expression was associated with a worse disease-free survival (DFS).Our results indicate that it is possible to define, through gene expression and computational analysis, a characteristic gene profiling of patients with an increased risk of relapse that may become a tool for patient selection for adjuvant therapy. PMID:27081700

  7. Antigenic Protein In Microgravity-Grown Human Mixed Mullerian Tumor (LN1) Cells Preserved In RNA Stabilizing Agent

    NASA Technical Reports Server (NTRS)

    Hammond, Dianne K.; Becker, Jeanne; Elliott, T. F.; Holubec, K.; Baker, T. L.; Love, J. E.

    2004-01-01

    Cells treated with RNAlater(TradeMark) have previously been shown to contain antigenic proteins that can be visualized using Western blot analysis. These proteins seem to be stable for several months when stored in RNA stabilizer at 4 C. Antigenic protein can be recovered from cells that have been processed using an Ambion RNAqueous(Registered TradeMark) kit to remove RNA. In this set of experiments, human mixed Mullerian tumor (LNI) cells grown on the International Space Station during Expedition 3 were examined for antigenic stability after removal of RNA. The cells were stored for three months in RNAlater(TradeMark) and RNA was extracted. The RNA filtrate containing the protein was precipitated, washed, and suspended in buffer containing sodium dodecyl sulfate (SDS). Samples containing equal concentrations of protein were loaded onto SDS-polyacrylamide gels. Proteins were separated by electrophoresis and transferred by Western blot to polyvinylidene fluoride (PVDF) membrane. The Western blots were stained with an enhanced chemiluminescent ECL(Registered Trademark) Plus detection kit (Amersham) and scanned using a Storm 840 gel image analyzer (Amersham, Molecular Dynamics). ImageQuant(Registered TradeMark) software was used to quantify the densities of the protein bands. The ground control and flight LN1 cell samples showed a similar staining pattern over time with antibodies to vimentin, glyceraldehyde-3-phosphate dehydrogenase, and epithelial membrane antigens.

  8. Antigenic Protein In Microgravity-Grown Human Mixed Mullerian Tumor (LN1) Cells Preserved In RNA Stabilizing Agent

    NASA Technical Reports Server (NTRS)

    Hammond, Dianne K.; Becker, Jeanne; Holubec, K.; Baker, T. L.; Love, J. E.

    2004-01-01

    Cells treated with RNAlater(TradeMark) have previously been shown to contain antigenic proteins that can be visualized using Western blot analysis. These proteins seem to be stable for several months when stored in RNA stabilizer at 4 C. Antigenic protein can be recovered from cells that have been processed using an Ambion RNAqueous(Registered TradeMark) kit to remove RNA. In this set of experiments, human mixed Mullerian tumor (LN1) cells grown on the International Space Station during Expedition 3 were examined for antigenic stability after removal of RNA. The cells were stored for three months in RNAlater(TradeMark) and RNA was extracted. The RNA filtrate Containing the protein was precipitated, washed, and suspended in buffer containing sodium dodecyl sulfate (SDS). Samples containing equal concentrations of protein were loaded onto SDS-polyacrylamide gels. Proteins were separated by electrophoresis and transferred by Western blot to polyvinylidene fluoride (PVDF) membrane. The Western blots were stained with an enhanced chemiluminescent ECL(Registered TradeMark)Plus detection kit (Amersham) and scanned using a Storm 840 gel image analyzer (Amersham, Molecular Dynamics). ImageQuant(Registered TradeMark)a software was used to quantify the densities of the protein bands. The ground control and flight LN1 cell samples showed a similar staining pattern over time with antibodies to vimentin, glyceraldehyde-3-phosphate dehydrogenase, and epithelial membrane antigens.

  9. Comparison of anti-mullerian hormone level in non-endometriotic benign ovarian cyst before and after laparoscopic cystectomy

    PubMed Central

    Amooee, Sedigheh; Gharib, Mahboubeh; Ravanfar, Parsa

    2015-01-01

    Background: Benign ovarian cysts are common among both pre- and postmenstrual women. Surgical intervention for excision of an ovarian cyst is mandated when symptomatic, or chance for malignancy is high. The damaging effect of surgical ovarian cystectomy on ovarian reserve is debated in recent studies. Objective: In the present study we investigated serum level of anti-mullerian hormone (AMH) as an indicator of ovarian reserve before and after surgical cystectomy. Materials and Methods: 60 patients with dermoid cyst, serous cystadenoma, and mucinous cystadenoma were recruited. Measurement of serum AMH was performed prior to surgery, and at one and 3 months after laparoscopic cystectomy. Serum AMH levels were compared before and after the surgery and between various types of ovarian cyst. Results: Serum AMH level declined significantly after the surgery which recovered to 65% of its baseline value three months later. Conclusion: Decreased serum AMH can be contributed to decreased ovarian reserve after laparoscopic ovarian cystectomy. This can result from thermo-coagulation used for hemostasis during the operation. PMID:26000005

  10. Three-dimensional culture of a mixed mullerian tumor of the ovary: expression of in vivo characteristics

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; Prewett, T. L.; Spaulding, G. F.; Becker, J. L.

    1997-01-01

    The Rotating-Wall Vessel (RWV) is a novel in vitro cell culture system used to successfully culture a cell line derived from a heterologous mixed mullerian tumor cell of the ovary. Although the original tumor was comprised of both epithelial and mesodermal components, long-term culture in conventional flasks established a cell line from this tumor with homogeneous epitheliallike growth characteristics (1). Cells from Passage 36 were seeded into a Rotating-Wall Vessel containing Cytodex-3 microcarrier beads. Scanning electron micrographs of tumor cells cultured for 32 d in the RWV showed the presence of heterogeneous cell populations organized into three-dimensional tissuelike architecture. Immunocytochemical analysis confirmed the cellular heterogeneity, as demonstrated by expression of both epithelial and mesenchymal antigens. Reverse transcription polymerase chain reaction amplification demonstrated the presence of mRNA for cellular oncogenes HER-2/neu, H-ras, K-ras, and tumor suppressor p53. Thus, there are two advantages to propagation of tissue in the RWV culture system:(a) tissue diversification representing populations present in the original tumor, and (b) the three-dimensional freedom to organize tissues morphologically akin to those observed in vivo. These data indicate that the RWV culture system is suitable for generating large quantities of ovarian tumor cells in vitro that are amenable to immunocytochemical, oncogenic, morphologic characteristics demonstrated in vivo.

  11. Can anti-Mullerian hormone replace ultrasonographic evaluation in polycystic ovary syndrome? A review of current progress

    PubMed Central

    Singh, Awadhesh Kumar; Singh, Ritu

    2015-01-01

    Several studies over the past decade have now consistently indicated that the serum anti-Mullerian hormone (AMH) levels are at least 2–3-fold higher in the patients with polycystic ovary syndrome (PCOS), which also corresponds to the increased number of AMH producing preantral and small antral follicles. Moreover, AMH levels have been found to be associated in direct proportion to the follicle numbers per ovary or antral follicular count, assessed by the transvaginal ultrasound (TVS). Furthermore, AMH correlates directly with the rising serum testosterone and luteinizing hormone levels in PCOS. Hence, serum AMH in women with oligo-anovulation and/or hyperandrogenemia could indicate the presence of underlying PCOS, when reliable TVS is not feasible, or not acceptable, either due to the virginal status or psycho-social issue. In addition, the imaging quality of abdominal ultrasound is often impaired by obesity, which typically occurs in PCOS women. Indeed, PCOS occurs most commonly in young females who cannot be subjected to invasive TVS for various reasons; therefore, a desirable alternative to TVS is urgently required to diagnose the most prevalent endocrine abnormality of young women. This review will analyze the currently available evidence regarding the role of AMH in the diagnosis of PCOS. PMID:26693422

  12. Is anti-mullerian hormone a marker of acute cyclophosphamide-induced ovarian follicular destruction in mice pretreated with cetrorelix?

    PubMed Central

    Browne, Hyacinth N.; Moon, Kimberly S.; Mumford, Sunni L.; Schisterman, Enrique F.; DeCherney, Alan H.; Segars, James H.; Armstrong, Alicia Y.

    2011-01-01

    Objective To define whether anti-mullerian hormone may be a marker of acute cyclophosphamide-induced germ cell destruction in mice pretreated with the GnRH antagonist, cetrorelix. Design Controlled, experimental study. Setting Research laboratory in a federal research facility. Animals Balb/c female mice (6 weeks old). Interventions Mice were treated with GnRH antagonist (cetrorelix) or saline for 15 days followed by 75 mg/kg or 100 mg/kg of cyclophosphamide or saline control on day 9. Main Outcome Measure(s) Number of primordial follicles (PMF), DNA damage, AMH protein expression, and AMH serum levels. Results Ovaries in mice pre-treated with cetrorelix had significantly more PMF and reduced DNA damage compared to those exposed to cyclophosphamide alone. Immunohistochemical staining for AMH expression and serum AMH levels did not differ significantly between treatment groups. Conclusions Cetrorelix protected primordial follicles and reduced DNA damage in follicles of mice treated with cyclophosphamide, but AMH levels in tissue and serum did not correlate with germ cell destruction. Further research is needed to determine the mechanism responsible for the protective effects on PMF counts observed with cetrorelix. PMID:21550044

  13. Systemic and local anti-Mullerian hormone reflects differences in the reproduction potential of Zebu and European type cattle.

    PubMed

    Carter, Anja Stojsin-; Mahboubi, Kiana; Costa, Nathalia N; Gillis, Daniel J; Carter, Timothy F; Neal, Michael S; Miranda, Moyses S; Ohashi, Otavio M; Favetta, Laura A; King, W Allan

    2016-04-01

    This study was conducted to evaluate plasma anti-Mullerian hormone (Pl AMH), follicular fluid AMH (FF AMH) and granulosa cell AMH transcript (GC AMH) levels and their relationships with reproductive parameters in two cattle subspecies, Bos taurus indicus (Zebu), and Bos taurus taurus (European type cattle). Two-dimensional ultrasound examination and serum collection were performed on Zebu, European type and crossbreed cows to determine antral follicle count (AFC), ovary diameter (OD) and Pl AMH concentration. Slaughterhouse ovaries for Zebu and European type cattle were collected to determine FF AMH concentrations, GC AMH RNA levels, AFC, oocyte number, cleavage and blastocyst rate. Additionally GC AMH receptor 2 (AMHR2) RNA level was measured for European type cattle. Relationship between AMH and reproductive parameters was found to be significantly greater in Zebu compared to European cattle. Average Pl AMH mean±SE for Zebu and European cattle was 0.77±0.09 and 0.33±0.24ng/ml respectively (p=0.01), whereas average antral FF AMH mean±SE for Zebu and European cattle was 4934.3±568.5 and 2977.9±214.1ng/ml respectively (p<0.05). This is the first published report of FF and GC AMH in Zebu cattle. Levels of GC AMHR2 RNA in European cattle were correlated to oocyte number (p=0.01). Crossbred animals were found more similar to their maternal Zebu counterparts with respect to their Pl AMH to AFC and OD relationships. These results demonstrate that AMH reflects differences between reproduction potential of the two cattle subspecies therefore can potentially be used as a reproductive marker. Furthermore these results reinforce the importance of separately considering the genetic backgrounds of animals when collecting or interpreting bovine AMH data for reproductive performance. PMID:26898391

  14. Anti-Mullerian hormone may be a useful adjunct in the diagnosis of polycystic ovary syndrome in nonobese adolescents

    PubMed Central

    Sopher, Aviva B.; Grigoriev, Galina; Laura, Diana; Cameo, Tamara; Lerner, Jodi P.; Chang, R. Jeffrey; McMahon, Donald J.; Oberfield, Sharon E.

    2015-01-01

    Objectives This study aimed to [1] confirm that nonobese adolescents with polycystic ovary syndrome (PCOS) have higher anti-Mullerian hormone (AMH) than controls; [2] examine the relationship of AMH with PCOS features and hormonal profile; and [3] approximate an AMH value that discriminates between adolescents with PCOS and controls. Design Case-control study. Setting Subspecialty ambulatory clinic. Patients Thirty-one nonobese adolescent girls (age 13–21 years), 15 with PCOS diagnosed using the National Institutes of Health (NIH) criteria and 16 healthy control subjects. Subjects and controls were comparable for body mass index z-score, age and ethnicity. Main outcome measure(s) AMH in PCOS subjects and control groups, correlation of AMH with hormonal parameters. Results AMH was higher in PCOS subjects (4.4 ±3.4 ng/mL) than in controls (2.4 ±1.3 ng/mL), when adjusted for menstrual age. In the entire group (PCOS and controls), AMH correlated with androgens, ovarian size and the presence of polycystic ovary (PCO) appearance. There was no difference in average ovarian size between PCOS (7.1 ±2.6 cm3) and controls (6.7 ±1.8 cm3). PCOS subjects were 1.49 times more likely to have AMH >3.4 ng/mL (confidence interval 0.98–2.26 ng/mL). Conclusions Our data suggest that AMH may be a useful adjunct in the diagnosis of PCOS in adolescents. PMID:25003376

  15. Anti-Mullerian hormone (AMH) concentration in follicular fluid and mRNA expression of AMH receptor type II and LH receptor in granulosa cells as predictive markers of good buffalo (Bubalus bubalis) donors.

    PubMed

    Liang, Aixin; Salzano, Angela; D'Esposito, Maurizio; Comin, Antonella; Montillo, Marta; Yang, Liguo; Campanile, Giuseppe; Gasparrini, Bianca

    2016-09-01

    High individual variability in follicular recruitment and hence in the number of embryos produced is a major factor limiting the application of reproductive technologies in buffalo. Therefore, the identification of reliable markers to select embryo donors is critical to enroll buffaloes in embryo production programs. Better understanding of factors involved in follicular growth is also necessary to improve the response to superovulation in this species. The aim of this work was thus to determine the anti-Mullerian hormone (AMH) concentration in follicular fluid (FF) recovered from different size follicles and evaluate the mRNA expression profiles of development-related (AMHR2, CYP19A1, FSHR, and LHR) and apoptosis-related genes (TP53INP1 and CASP3) in the corresponding granulosa cells (GCs) in buffalo. Another objective was to evaluate whether the AMH concentration in FF and gene expression of GCs is associated with the antral follicular count. Ovaries were collected at the slaughterhouse, and all follicles were counted and classified as small (3-5 mm), medium (5-8 mm), and large (>8 mm). Follicular fluid was recovered for AMH determination, and the mRNA expression of AMHR2, FSHR, LHR, CYP19A1, TP53INP1, and CASP3 was analyzed in GCs. The AMH concentration in FF decreased (P < 0.01) at increasing follicular diameter. The mRNA expression of AMHR2 and FSHR was higher (P < 0.05) in small follicles, whereas that of LHR and CYP19A1 was higher (P < 0.05) in large follicles. The intrafollicular AMH concentration was positively correlated with the antral follicular count (r = 0.31; P < 0.05). Interestingly, good donors (≥12 follicles) had a higher (P < 0.05) concentration of AMH and AMHR2 levels in small follicles and higher (P < 0.05) LHR levels in large follicles than bad donors (<12 follicles). These results suggest a potential use of AMH to select buffalo donors to enroll in embryo production programs, laying the basis for further investigations

  16. Anti-Mullerian hormone trend evaluation after laparoscopic surgery of monolateral endometrioma using a new dual wavelengths laser system (DWLS) for hemostasis.

    PubMed

    Nappi, Luigi; Angioni, Stefano; Sorrentino, Felice; Cinnella, Gilda; Lombardi, Michela; Greco, Pantaleo

    2016-01-01

    Operative laparoscopy is the gold standard in the treatment of endometriotic ovarian cysts. Excisional surgery is the best technique to prevent recurrences and improve symptoms but it may result in ovarian reserve damage due to the removal of healthy ovarian cortex. The aim of this study was to assess the impact on ovarian reserve of the use of dual wavelengths laser system (DWLS) hemostasis after stripping technique of monolateral endometrioma, by dosing the anti-Mullerian hormone (AMH). This prospective study was conducted at the Institute of Obstetrics and Gynecology, University of Foggia, from December 2013 to January 2015. Forty-five women underwent excision of monolateral endometriotic ovarian cyst by stripping without using a bipolar coagulation and performing hemostasis with a DWLS. The AMH serum levels were estimated before the surgery (T0), 4-6 weeks (T1) and 6-9 months (T2) after surgery. Our results suggest that an appropriate surgical technique with the use of laser hemostasis does not determine a significant reduction of ovarian reserve. Laser hemostasis could prevent follicular reserve loss after ovarian endometrioma surgery. PMID:26359914

  17. Serum Copeptin, Pentraxin 3, Anti-Mullerian Hormone Levels With Echocardiography and Carotid Artery Intima-Media Thickness in Adolescents With Polycystic Ovary Syndrome

    PubMed Central

    Deveer, Mehmet; Deveer, Ruya; Basaran, Ozcan; Turkcu, Ummuhani Ozel; Akbaba, Eren; Cullu, Nesat; Turhan, Nilgun; Kucuk, Mert; Kasap, Burcu

    2015-01-01

    Background The aim of the study was to investigate the presence of possible markers in the prediction of polycystic ovary syndrome (PCOS)-related metabolic alterations and cardiovascular events in adolescent PCOS cases and also to investigate the applicability of anti-Mullerian hormone (AMH) levels for the diagnosis of PCOS. Methods In this cross-sectional study, a total of 75 non-obese women (adolescent PCOS group, n = 25; adult PCOS group, n = 25; control group, n = 25) were included. Measurements of copeptin, pentraxin 3 (PTX3), and AMH serum levels were performed. Results Serum copeptin, PTX3 and echocardiographic indices were not significantly different in PCOS subjects and they did not have higher common carotid artery intima-media thickness (CIMT) measurement. AMH levels were significantly higher in PCOS patients. There was a positive correlation between AMH and mean ovarian volume (r = 0.58, P < 0.001) and between AMH and total testosterone level (r = 0.63, P < 0.001). In order to predict a threshold value for the diagnosis of PCOS by using AMH, the receiver operating characteristic (ROC) method was used. Area under the curve was 0.820 and cut-off point was 6.66 ng/mL for AMH with a sensitivity of 62% and specificity of 76%. Conclusions Possible markers for PCOS-related metabolic alterations may not present in the adolescent years. Serum AMH may be useful as a diagnostic test for adolescents. PMID:26566413

  18. Role of Baseline Antral Follicle Count and Anti-Mullerian Hormone in Prediction of Cumulative Live Birth in the First In Vitro Fertilisation Cycle: A Retrospective Cohort Analysis

    PubMed Central

    Li, Hang Wun Raymond; Lee, Vivian Chi Yan; Lau, Estella Yee Lan; Yeung, William Shu Biu; Ho, Pak Chung; Ng, Ernest Hung Yu

    2013-01-01

    Objective This retrospective study determined for the first time the role of baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the first in-vitro fertilisation (IVF) cycle in predicting cumulative live birth from one stimulation cycle. Methods We studied 1,156 women (median age 35 years) undergoing the first IVF cycle. Baseline AFC and AMH level on the day before ovarian stimulation were analysed. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers after the same stimulation cycle. Results Serum AMH was significantly correlated with AFC. Both AMH and AFC showed significant correlation with age and ovarian response in the stimulated cycle and total number of transferrable embryos. Baseline AFC and serum AMH were significantly higher in subjects attaining a live birth than those who did not in the fresh stimulated cycle, as well as those attaining cumulative live birth. There was a significant trend of higher cumulative live birth rate in women with higher AMH or AFC. However, logistic regression revealed that both AMH and AFC were not significant predictors of cumulative live birth after adjusting for age and number of embryos available for transfer. Considering only one single predictor, the areas under the ROC curves for AMH (0.646, 95% CI 0.616–0.675) and age (0.648, 95% CI 0.618–0.677) were slightly higher than that for AFC (0.617, 95% CI 0.587–0.647) in predicting cumulative live birth. However, a model combining AMH (with or without AFC) and age of the women only classified an addition of less than 2% of subjects correctly compared to the model with age alone. Conclusion Baseline AFC and serum AMH have only modest predictive performance on the occurrence of cumulative live birth, and may not give additional value on top of the women's age. PMID:23637787

  19. Effects of GnRH agonists on the expression of developmental follicular anti-mullerian hormone in varying follicular stages in cyclic mice in vivo

    PubMed Central

    HUANG, JILIANG; WANG, XIAOYAN; LI, ZHILING; MA, RUOWU; XIAO, WANFEN

    2015-01-01

    Gonadotrophin-releasing hormone (GnRH) agonists (GnRHa) have been widely used to induce a state of downregulation for in vitro fertilization, and its direct effects on the pituitary are well known. However, the effects of GnRHa on the expression of anti-mullerian hormone (AMH) by follicles in varying stages in vivo remain to be fully elucidated. In the present study 84 cyclic mice were randomly divided equally into four GnRHa groups and three cyclic mice were used as a control group. The expression levels of AMH in follicles of varying stages between days 0 and 7 following GnRHa administration were quantified using immunohistochemistry. The expression of AMH in follicles at various stages revealed dynamic changes during the process of downregulation. AMH in primary follicles initially increased and then decreased gradually. In small and large preantral follicles and in granulosa cells (GCs) surrounding the oocyte of small antral follicles, the expression of AMH began to increase on day 1, was attenuated on day 2, and then increased to a peak. The expression levels of AMH in the GCs surrounding the basement membrane, in contrast to the GCs surrounding the oocyte, were significantly lower and did not increase on day 1. In all stages of follicles, the expression of AMH declined gradually between the peak level and last day of downregulation. On day 7, the varying follicular stages all expressed lower levels of AMH than on day 0. This decrease was more prominent in the higher dose groups, compared with the lower dose groups. In conclusion, GnRHa was observed to induce time-dependent changes in the expression of AMH at varying follicular stages, which occurred in a dose-dependent manner. PMID:26126720

  20. The Correlations of Anti-Mullerian Hormone, Follicle-Stimulating Hormone and Antral Follicle Count in Different Age Groups of Infertile Women

    PubMed Central

    Barbakadze, Ludmila; Kristesashvili, Jenara; Khonelidze, Natalia; Tsagareishvili, Gia

    2015-01-01

    Background The objective of our study was to identify the correlations between the tests currently used in ovarian reserve assessment: anti-Mullerian hormone (AMH), follicle stimulating hormone (FSH) and antral follicle count (AFC) and to distinguish the most reliable markers for ovarian reserve in order to select an adequate strategy for the initial stages of infertility treatment. Materials and Methods In this prospective study, 112 infertile women were assessed. Subjects were divided into three age groups: group I <35 years (n=39), group II 35-40 years (n=31), and group III 41-46 years (n=42). AMH, FSH and AFC were determined on days 2-3 of the patients’ menstrual cycles. Results There was a significantly elevated negative correlation between age and AMH level (rs=-0.67, p<0.0001) and AFC (rs=-0.55, p<0.0001). We observed a significantly positive correlation between age and FSH (rs=0.38, p<0.0001). AMH negatively correlated with FSH (rs=-0.48, p<0.0001) and positively with AFC (r=-0.71, p=0.0001). There was a moderate negative relation between FSH and AFC (r=-0.41, p=0.0001) and moderate positive relation between age and FSH (rs=0.38, p<0.0001). The correlation analysis performed in separate groups showed that AMH and AFC showed a statistically significant positive correlation for group I (r=0.57, p<0.0001), group II (r=0.69, p<0.0001) and group III (r=0.47, p<0.002). A statistically significant correlation between FSH and AMH was detected only in groups I (r=-0.41, p<0.02) and II (r=-0.55, p<0.0001). A statistically significant correlation existed between FSH and AFC only in group III (r=-0.42, p<0.006), as well as between age and AFC only in group I (r=-0.35, p<0.03). Conclusion Currently, AMH should be considered as the more reliable of the ovarian reserve assessments tests compared to FSH. There is a strong positive correlation between serum AMH level and AFC. The use of AMH combined with AFC may improve ovarian reserve evaluation. PMID:25780521

  1. Inhibition of fetal bone development through epigenetic down- regulation of HoxA10 in obese rats fed high fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological studies show that maternal obesity during intrauterine and early postnatal life increases the risk of low bone mass and fracture later in life. Here, we show that bone development is inhibited in GED 18.5 embryos from rat dams made obese by feeding a high fat diet (HFD). Moreover, fe...

  2. Ovarian Response and Cumulative Live Birth Rate of Women Undergoing In-Vitro Fertilisation Who Had Discordant Anti-Mullerian Hormone and Antral Follicle Count Measurements: A Retrospective Study

    PubMed Central

    Li, Hang Wun Raymond; Lee, Vivian Chi Yan; Lau, Estella Yee Lan; Yeung, William Shu Biu; Ho, Pak Chung; Ng, Ernest Hung Yu

    2014-01-01

    Objective To evaluate ovarian response and cumulative live birth rate of women undergoing in-vitro fertilization (IVF) treatment who had discordant baseline serum anti-Mullerian hormone (AMH) level and antral follicle count (AFC). Methods This is a retrospective cohort study on 1,046 women undergoing the first IVF cycle in Queen Mary Hospital, Hong Kong. Subjects receiving standard IVF treatment with the GnRH agonist long protocol were classified according to their quartiles of baseline AMH and AFC measurements after GnRH agonist down-regulation and before commencing ovarian stimulation. The number of retrieved oocytes, ovarian sensitivity index (OSI) and cumulative live-birth rate for each classification category were compared. Results Among our studied subjects, 32.2% were discordant in their AMH and AFC quartiles. Among them, those having higher AMH within the same AFC quartile had higher number of retrieved oocytes and cumulative live-birth rate. Subjects discordant in AMH and AFC had intermediate OSI which differed significantly compared to those concordant in AMH and AFC on either end. OSI of those discordant in AMH and AFC did not differ significantly whether either AMH or AFC quartile was higher than the other. Conclusions When AMH and AFC are discordant, the ovarian responsiveness is intermediate between that when both are concordant on either end. Women having higher AMH within the same AFC quartile had higher number of retrieved oocytes and cumulative live-birth rate. PMID:25313856

  3. Estimates of Selection and Gene Flow from Measures of Cline Width and Linkage Disequilibrium in Heliconius Hybrid Zones

    PubMed Central

    Mallet, J.; Barton, N.; Gerardo, L. M.; Jose, S. C.; Manuel, M. M.; Eeley, H.

    1990-01-01

    Hybrid zones can yield estimates of natural selection and gene flow. The width of a cline in gene frequency is approximately proportional to gene flow (σ) divided by the square root of per-locus selection ( &s). Gene flow also causes gametic correlations (linkage disequilibria) between genes that differ across hybrid zones. Correlations are stronger when the hybrid zone is narrow, and rise to a maximum roughly equal to s. Thus cline width and gametic correlations combine to give estimates of gene flow and selection. These indirect measures of σ and s are especially useful because they can be made from collections, and require no field experiments. The method was applied to hybrid zones between color pattern races in a pair of Peruvian Heliconius butterfly species. The species are Mullerian mimics of one another, and both show the same changes in warning color pattern across their respective hybrid zones. The expectations of cline width and gametic correlation were generated using simulations of clines stabilized by strong frequency-dependent selection. In the hybrid zone in Heliconius erato, clines at three major color pattern loci were between 8.5 and 10.2 km wide, and the pairwise gametic correlations peaked at R & 0.35. These measures suggest that s & 0.23 per locus, and that σ & 2.6 km. In erato, the shapes of the clines agreed with that expected on the basis of dominance. Heliconius melpomene has a nearly coincident hybrid zone. In this species, cline widths at four major color pattern loci varied between 11.7 and 13.4 km. Pairwise gametic correlations peaked near R & 1.00 for tightly linked genes, and at R & 0.40 for unlinked genes, giving s & 0.25 per locus and σ & 3.7 km. In melpomene, cline shapes did not perfectly fit theoretical shapes based on dominance; this deviation might be explained by long-distance migration and/or strong epistasis. Compared with erato, sample sizes in melpomene are lower and the genetics of its color patterns are less well

  4. Genes and Gene Therapy

    MedlinePlus

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  5. Genes and Gene Therapy

    MedlinePlus

    ... a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  6. Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human

    SciTech Connect

    Mbikay, M.; Seidah, N.G.; Chretien, M.

    1995-03-01

    The genes for three subtilisin/kexin-like proprotein convertases, PC4, PC5, and PACE4, were mapped in the mouse by RFLP analysis of a DNA panel from a (C57BL/6JEi x SPRET/Ei) F{sub 1} x SPRET/Ei backcross. The chromosomal locations of the human homologs were determined by Southern blot analysis of a DNA panel from human-rodent somatic cell hybrids, most of which contained a single human chromosome each. The gene for PC4 (Pcsk4 locus) mapped to mouse chromosome 10, close to the Adn (adipsin, a serine protease) locus and near the Amh (anti-Mullerian hormone) locus; in a human, the gene was localized to chromosome 19. The gene for PC5 (Pcsk5 locus) mapped to mouse chromosome 19 close to the Lpc1 (lipoacortin-1) locus and, in human, was localized to chromosome 9. The gene for PACE4 (Pcsk6 locus) mapped to mouse chromosome 7, at a distance of 13 cM from the Pcsk3 locus, which specifies furin, another member of this family of enzymes previoulsy mapped to this chromosome. This is in concordance with the known close proximity of these two loci in the homologous region on human chromosome 15q25-qter. Pcsk3 and Pcsk6 mapped to a region of mouse chromosome 7 that has been associated cytogenetically with postnatal lethality in maternal disomy, suggesting that these genes might be candidates for imprinting. 43 refs., 3 figs., 2 tabs.

  7. Prepubertal bisphenol A exposure interferes with ovarian follicle development and its relevant gene expression.

    PubMed

    Li, Yuchen; Zhang, Wenchang; Liu, Jin; Wang, Wenxiang; Li, Hong; Zhu, Jianling; Weng, Shaozheng; Xiao, Shihua; Wu, Tingting

    2014-04-01

    Bisphenol A (BPA) is recognized as one of several environmental estrogens. Pre-puberty is an important part of reproductive system development, and even a short-term exposure to BPA during this period may cause serious damage to the reproductive system. In this study, Pre-puberty female Wistar rats were exposed to BPA for one week. The effects of BPA on ovarian structure and function were assessed. The expression levels of follicle development-related genes were analyzed. Our study showed that BPA reduced rat ovarian weights and follicle numbers, and interferes with the constituent ratio of follicles. With increasing doses of BPA, the expression of factor in the germline alpha (FIGLA) and oocyte-specific histone H1 variant (H1FOO) genes decreased, and anti-mullerian hormone (AMH) genes expression increased, suggesting that BPA exposure during the pre-pubertal period may inhibit the development of ovaries, and follicle development-related genes may play certain roles in this process. PMID:24051130

  8. Serous carcinomatous component championed by heparin-binding EGF-like growth factor (HB-EGF) predisposing to metastasis and recurrence in stage I uterine malignant mixed mullerian tumor.

    PubMed

    Zhang, Lei; Shimizu, David; Killeen, Jeffrey L; Honda, Stacey A; Lu, Di; Stanoyevitch, Alexander; Lin, Fritz; Wang, Beverly; Monuki, Edwin S; Carbone, Michele

    2016-07-01

    The stage I uterine malignant mixed mullerian tumor (MMMT) shows different potential for progression. We reason that MMMTs with high-grade carcinomatous component and positivity for HB-EGF are prone to recurrence/metastasis in the early stage. A retrospective clinical and histopathologic review with immunohistochemical staining for HB-EGF, EGFR, and integrin-α5 was performed for 62 surgically staged MMMT cases. Recurrence/metastasis (RM) is 6/18 (33%) in stage I disease. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component (83% [5/6] versus 17% [1/12], P = .0015) and HB-EGF expression (100% [6/6] versus 50% [6/12], P=.0339) were significantly different between groups with RM and without RM. The presence of serous carcinoma in all stages was 83% (5/6) in stage I with RM, 8% (1/12) in stage I without RM, 20% (1/5) in stage II, 36.4% (8/22) in stage III and 64.7% (11/17) in stage IV; this was paralleled by HB-EGF expression of 100% (6/6), 50% (6/12), 40% (2/5), 50% (11/22) and 71% (12/17) with a correlation coefficient r=0.9131 (P=.027). HB-EGF and integrin-α5 were highly expressed in MMMTs bearing serous carcinoma component, compared to endometrioid and unclassifiable/miscellaneous subtypes (84.6%/47.6%/33.3%, P=.025 for HB-EGF; and 61.5%/42.9%/20.0%, P=.021 for integrin-α5). The EGFR positivity was comparable among the three subtypes (48.1%, 47.6% and 26.7%, P=.326). This study indicates that serous carcinomatous component championed by expression of HB-EGF predisposes to recurrence/metastasis in stage I MMMT. This process might involve integrin-α5 and does not seem to require overexpression of EGFR. Further study is required. PMID:26980026

  9. Gene Alterations of Ovarian Cancer Cells Expressing Estrogen Receptors by Estrogen and Bisphenol A Using Microarray Analysis

    PubMed Central

    Hwang, Kyung-A; Park, Se-Hyung; Yi, Bo-Rim

    2011-01-01

    Since endocrine disrupting chemicals (EDCs) may interfere with the endocrine system(s) of our body and have an estrogenicity, we evaluated the effect(s) of bisphenol A (BPA) on the transcriptional levels of altered genes in estrogen receptor (ER)-positive BG-1 ovarian cancer cells by microarray and real-time polymerase-chain reaction. In this study, treatment with 17β-estradiol (E2) or BPA increased mRNA levels of E2-responsive genes related to apoptosis, cancer and cell cycle, signal transduction and nucleic acid binding etc. In parallel with their microarray data, the mRNA levels of some altered genes including RAB31_MEMBER RAS ONCOGENE FAMILY (U59877), CYCLIN D1 (X59798), CYCLIN-DEPENDENT KINASE 4 (U37022), IGF-BINDING PROTEIN 4 (U20982), and ANTI-MULLERIAN HORMONE (NM_000479) were significantly induced by E2 or BPA in this cell model. These results indicate that BPA in parallel with E2 induced the transcriptional levels of E2-responsive genes in an estrogen receptor (ER)-positive BG-1 cells. In conclusion, these microarray and real-time polymerase-chain reaction results indicate that BPA, a potential weak estrogen, may have estrogenic effect by regulating E2-responsive genes in ER-positive BG-1 cells and BG-1 cells would be the best in vitro model to detect these estrogenic EDCs. PMID:21826169

  10. Ovarian reserve status in young women is associated with altered gene expression in membrana granulosa cells

    PubMed Central

    Skiadas, Christine C.; Duan, Shenghua; Correll, Mick; Rubio, Renee; Karaca, Nilay; Ginsburg, Elizabeth S.; Quackenbush, John; Racowsky, Catherine

    2012-01-01

    Diminished ovarian reserve (DOR) is a challenging diagnosis of infertility, as there are currently no tests to predict who may become affected with this condition, or at what age. We designed the present study to compare the gene expression profile of membrana granulosa cells from young women affected with DOR with those from egg donors of similar age and to determine if distinct genetic patterns could be identified to provide insight into the etiology of DOR. Young women with DOR were identified based on FSH level in conjunction with poor follicular development during an IVF cycle (n = 13). Egg donors with normal ovarian reserve (NOR) comprised the control group (n = 13). Granulosa cells were collected following retrieval, RNA was extracted and microarray analysis was conducted to evaluate genetic differences between the groups. Confirmatory studies were undertaken with quantitative RT–PCR (qRT–PCR). Multiple significant differences in gene expression were observed between the DOR patients and egg donors. Two genes linked with ovarian function, anti-Mullerian hormone (AMH) and luteinizing hormone receptor (LHCGR), were further analyzed with qRT–PCR in all patients. The average expression of AMH was significantly higher in egg donors (adjusted P-value = 0.01), and the average expression of LHCGR was significantly higher in DOR patients (adjusted P-value = 0.005). Expression levels for four additional genes, progesterone receptor membrane component 2 (PGRMC2), prostaglandin E receptor 3 (subtype EP3) (PTGER3), steroidogenic acute regulatory protein (StAR), and StAR-related lipid transfer domain containing 4 (StarD4), were validated in a group consisting of five NOR and five DOR patients. We conclude that gene expression analysis has substantial potential to determine which young women may be affected with DOR. More importantly, our analysis suggests that DOR patients fall into two distinct subgroups based on gene expression profiles, indicating that different

  11. Genes and gene regulation

    SciTech Connect

    MacLean, N.

    1988-01-01

    Genetics has long been a central topic for biologists, and recent progress has captured the public imagination as well. This book addresses questions that are at the leading edge of this continually advancing discipline. In tune with the increasing emphasis on molecular biology and genetic engineering, this text emphasizes the molecular aspects of gene expression, and the evolution of gene sequence organization and control. It reviews the genetic material of viruses, bacteria, and of higher organisms. Cells and organisms are compared in terms of gene numbers, their arrangements within a cell, and the control mechanisms which regulate the activity of genes.

  12. Studying Genes

    MedlinePlus

    ... Area What are genes? Genes are sections of DNA that contain instructions for making the molecules—many ... material in an organism. This includes genes and DNA elements that control the activity of genes. Does ...

  13. Antimullerian Hormone and Its Receptor Gene Expression in Prenatally Androgenized Female Rats

    PubMed Central

    Daneshian, Zahra; Ramezani Tehrani, Fahimeh; Zarkesh, Maryam; Norooz Zadeh, Mahsa; Mahdian, Reza; Zadeh Vakili, Azita

    2015-01-01

    Background: Anti-mullerian hormone (AMH) levels reflect the number of small antral follicles in ovaries and expression changes of AMH and its receptor are suspected to be involved in the pathogenesis of polycystic ovary syndrome (PCOS). Objectives: The aim of this study was to evaluate gene expression of AMH and its receptor in immature and adult rats prenatally exposed to androgen excess. Materials and Methods: Six pregnant Wistar rats in the experimental group were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 6) received only 500 mL of solvent. Female pups of each mother were randomly divided into three groups as day 0 (newborn), 10-day old and days 75-85 (adult). RNAs were extracted from ovarian tissues and relative expression levels for AMH and its receptor genes were measured using TaqMan Real-Time PCR. Serum AMH and testosterone levels were measured using ELISA method. Results: Relative AMH expression decreased in newborns, 10-day olds and adults (0.806, 0.443 and 0.809 fold, respectively). AMHR expression was higher in newborns and adults (1.432 and 1.057 fold, respectively), while it decreased by 0.263 fold in 10-day olds, although none of them were significant (P > 0.05). In addition, AMH levels were consistent with the results of gene expression. Testosterone hormone levels from 10 day-olds to adults were significantly increased in both study groups (P = 0.016). Conclusions: While AMH receptor expression was higher in experimental rats, their serum concentrations of AMH were decreased. Further researches with greater sample sizes and measurement of bioactive forms of hormones are recommended to confirm the findings of this study. PMID:25745494

  14. Loss of oocytes due to conditional ablation of Murine double minute 2 (Mdm2) gene is p53-dependent and results in female sterility.

    PubMed

    Livera, Gabriel; Uzbekov, Rustem; Jarrier, Peggy; Fouchécourt, Sophie; Duquenne, Clotilde; Parent, Anne-Simone; Marine, Jean-Christophe; Monget, Philippe

    2016-08-01

    Murine double minute 2 and 4 (Mdm2, Mdm4) are major p53-negative regulators, preventing thus uncontrolled apoptosis induction in numerous cell types, although their function in the female germ line has received little attention. In the present work, we have generated mice with specific invalidation of Mdm2 and Mdm4 genes in the mouse oocyte (Mdm2(Ocko) and Mdm4(Ocko) mice), to test their implication in survival of these germ cells. Most of the Mdm2(Ocko) but not Mdm4(Ocko) mice were sterile, with a dramatic reduction of the weight of ovaries and genital tract, a strong increase in follicle-stimulating hormone and luteinizing hormone serum levels, and a reduction of anti-mullerian hormone serum levels. Histological analyses revealed an obvious decrease of the number of growing follicles beyond the primary stage in Mdm2(Ocko) ovaries in comparison to controls, with a pronounced increase in the apparition of primary atretic follicles, most being devoid of oocyte. Similar phenotypes were observed with Mdm2(Ocko) Mdm4(Ocko) ovaries, with no worsening of the phenotype. However, we failed to detect any increase in p53 level in mutant oocytes, nor any other apoptotic marker, introgression of this targeted invalidation in p53-/- mice restored the fertility of females. This study is the first to show that Mdm2, but not Mdm4, has a critical role in oocyte survival and would be involved in premature ovarian insufficiency phenotype. PMID:27364741

  15. Developmental Methoxychlor Exposure Affects Multiple Reproductive Parameters and Ovarian: Folliculogenesis and Gene Expression in Adult Rats

    PubMed Central

    Armenti, AnnMarie E.; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-01-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 μg/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post-coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P < 0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P < 0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P < 0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor β was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P < 0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P < 0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis. PMID:18848953

  16. Developmental methoxychlor exposure affects multiple reproductive parameters and ovarian folliculogenesis and gene expression in adult rats

    SciTech Connect

    Armenti, AnnMarie E.; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-12-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 {mu}g/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P < 0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P < 0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P < 0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor {beta} was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P < 0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P < 0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis.

  17. Gene Therapy

    PubMed Central

    Baum, Bruce J

    2014-01-01

    Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases. PMID:24372817

  18. Trichoderma genes

    DOEpatents

    Foreman, Pamela; Goedegebuur, Frits; Van Solingen, Pieter; Ward, Michael

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  19. [Language gene].

    PubMed

    Takahashi, Hiroshi

    2006-11-01

    The human capacity for acquiring speech and language must derive, at least in part, from the genome. Recent advance in the field of molecular genetics finally discovered 'Language Gene'. Disruption of FOXP2 gene, the firstly identified 'language gene' causes severe speech and language disorder. To elucidate the anatomical basis of language processing in the brain, we examined the expression pattern of FOXP2/Foxp2 genes in the monkey and rat brains through development. We found the preferential expression of FOXP2/Foxp2 in the striosomal compartment of the developing striatum. Thus, we suggest the striatum, particularly striosomal system may participate in neural information processing for language and speech. Our suggestion is consistent with the declarative/ procedural model of language proposed by Ullman (1997, 2001), which the procedural memory-dependent mental grammar is rooted in the basal ganglia and the frontal cortex, and the declarative memory-dependent mental lexicon is rooted in the temporal lobe. PMID:17432197

  20. Genes V.

    SciTech Connect

    Lewin, B.

    1994-12-31

    This fifth edition book encompasses a wide range of topics covering 1,272 pages. The book is arranged into nine parts with a total of 36 chapters. These nine parts include Introduction; DNA as a Store of Information; Translation; Constructing Cells; Control of Prokaryotypic Gene Expression; Perpetuation of DNA; Organization of the Eukaryotypic Genome; Eukaryotypic Transcription and RNA Processing; The Dynamic Genome; and Genes in Development.

  1. Attention Genes

    ERIC Educational Resources Information Center

    Posner, Michael I.; Rothbart, Mary K.; Sheese, Brad E.

    2007-01-01

    A major problem for developmental science is understanding how the cognitive and emotional networks important in carrying out mental processes can be related to individual differences. The last five years have seen major advances in establishing links between alleles of specific genes and the neural networks underlying aspects of attention. These…

  2. Designer Genes.

    ERIC Educational Resources Information Center

    Miller, Judith; Miller, Mark

    1983-01-01

    Genetic technologies may soon help fill some of the most important needs of humanity from food to energy to health care. The research of major designer genes companies and reasons why the initial mad rush for biotechnology has slowed are reviewed. (SR)

  3. Anti-Mullerian-hormone levels during pregnancy and postpartum

    PubMed Central

    2013-01-01

    Background The number of unintentionally childless couples is increasing as more couples seek to conceive for the first time in the third or fourth decade of the woman’s life. Determination of ovarian reserve is an essential component of infertility assessment. The Anti-Müllerian-Hormone (AMH) seems to be the most reliable predictor of ovarian reserve. In this study we analyzed AMH in a cohort of pregnant women without fertility impairment to determine age-dependent decline and possible AMH fluctuations during pregnancy and postpartum. Methods A total of 554 healthy women aged 16 to 47 years without history of infertility or previous surgery on the ovaries were enrolled in the study between 1995 and 2012. In 450 women, a single measurement of AMH was taken during pregnancy, allowing for cross sectional analysis of trimester- and age-related differences in AMH levels. For another 15 women longitudinal data on AMH levels for all trimesters was recorded. In addition, for 69 women AMH was measured at the time just before and after delivery, and for another 20 AMH was measured just before delivery and once on each of the first four days after delivery. We used AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, USA) for the assessment of AMH levels. Non-parametric statistical tests were used to compare AMH levels between age groups, trimesters and postpartum. Results Comparison between the trimesters revealed a significant difference in AMH values at each trimester (first trimester: 1.69 ng/ml (IQR 0.71–3.10), second trimester: 0.8 ng/ml (IQR 0.48–1.41), third trimester: 0.5 ng/ml (IQR 0.18–1.00)). AMH significantly dropped during the course of pregnancy and immediately after delivery, whereas an increase was observed over the first four days postpartum. Women, greater than or equal to 35 years, showed significant lower AMH levels than those <35 years across all trimesters. Conclusions AMH levels decrease during pregnancy. The decline in AMH levels during pregnancy indicates ovarian suppression. AMH levels recover quickly after delivery. AMH levels assessed in pregnant women are not an accurate indicator of ovarian reserve, since AMH levels during pregnancy seem not to be independent of gestational age. PMID:23844593

  4. Genes and Hearing Loss

    MedlinePlus

    ... Meeting Calendar Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  5. Compare Gene Profiles

    SciTech Connect

    2014-05-31

    Compare Gene Profiles (CGP) performs pairwise gene content comparisons among a relatively large set of related bacterial genomes. CGP performs pairwise BLAST among gene calls from a set of input genome and associated annotation files, and combines the results to generate lists of common genes, unique genes, homologs, and genes from each genome that differ substantially in length from corresponding genes in the other genomes. CGP is implemented in Python and runs in a Linux environment in serial or parallel mode.

  6. Gene gymnastics

    PubMed Central

    Vijayachandran, Lakshmi S; Thimiri Govinda Raj, Deepak B; Edelweiss, Evelina; Gupta, Kapil; Maier, Josef; Gordeliy, Valentin; Fitzgerald, Daniel J; Berger, Imre

    2013-01-01

    Most essential activities in eukaryotic cells are catalyzed by large multiprotein assemblies containing up to ten or more interlocking subunits. The vast majority of these protein complexes are not easily accessible for high resolution studies aimed at unlocking their mechanisms, due to their low cellular abundance and high heterogeneity. Recombinant overproduction can resolve this bottleneck and baculovirus expression vector systems (BEVS) have emerged as particularly powerful tools for the provision of eukaryotic multiprotein complexes in high quality and quantity. Recently, synthetic biology approaches have begun to make their mark in improving existing BEVS reagents by de novo design of streamlined transfer plasmids and by engineering the baculovirus genome. Here we present OmniBac, comprising new custom designed reagents that further facilitate the integration of heterologous genes into the baculovirus genome for multiprotein expression. Based on comparative genome analysis and data mining, we herein present a blueprint to custom design and engineer the entire baculovirus genome for optimized production properties using a bottom-up synthetic biology approach. PMID:23328086

  7. Gene doping: gene delivery for olympic victory

    PubMed Central

    Gould, David

    2013-01-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called ‘gene doping’. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place. PMID:23082866

  8. Autism and Genes

    ERIC Educational Resources Information Center

    National Institutes of Health, 2005

    2005-01-01

    This document defines and discusses autism and how genes play a role in the condition. Answers to the following questions are covered: (1) What are genes? (2) What is autism? (3) What causes autism? (4) Why study genes to learn about autism? (5) How do researchers look for the genes involved in autism? (screen the whole genome; conduct cytogenetic…

  9. Compare Gene Profiles

    Energy Science and Technology Software Center (ESTSC)

    2014-05-31

    Compare Gene Profiles (CGP) performs pairwise gene content comparisons among a relatively large set of related bacterial genomes. CGP performs pairwise BLAST among gene calls from a set of input genome and associated annotation files, and combines the results to generate lists of common genes, unique genes, homologs, and genes from each genome that differ substantially in length from corresponding genes in the other genomes. CGP is implemented in Python and runs in a Linuxmore » environment in serial or parallel mode.« less

  10. Myeloid ecotropic viral integration site 1 (MEIS) 1 involvement in embryonic implantation

    PubMed Central

    Xu, Bei; Geerts, Dirk; Qian, Kun; Zhang, Hanwang; Zhu, Guijin

    2008-01-01

    BACKGROUND The HOXA10 homeobox gene controls embryonic uterine development and adult endometrial receptivity. The three-amino-acid loop extension (TALE) family homeobox genes like myeloid ecotropic viral integration site 1 (MEIS) provide enhanced target gene activation and specificity in HOX-regulated cellular processes by acting as HOX cofactors. METHODS AND RESULTS Analysis of an Affymetrix data set in the public domain showed high expression of MEIS1 in human endometrium. MEIS1 expression was confirmed during the human menstrual cycle by RT–PCR and in situ hybridization and was increased during the secretory compared with proliferative phase of the cycle (P = 0.0001), the time of implantation. To assess the importance of maternal Meis1 expression in a mouse model, the uteri of Day 2 pregnant mice were injected with Meis1 over-expression or small interfering RNA (siRNA) constructs. Blocking Meis1 expression by siRNA before implantation significantly reduced average implantation rates (P = 0.00001). Increased or decreased Meis1 expression significantly increased or decreased the expression of integrin β3, a transcriptional target of HOXA10 and an important factor in early embryo-endometrium interactions (P = 0.006). Manipulating Meis1 expression before implantation also dramatically affected the number of pinopodes, uterine endometrial epithelial projections that develop at the time of endometrial receptivity. CONCLUSIONS The results suggest that in mouse, meis1 contributes to regulating endometrial development during the menstrual cycle and establishing the conditions necessary for implantation. PMID:18408019

  11. Evolution by gene loss.

    PubMed

    Albalat, Ricard; Cañestro, Cristian

    2016-07-01

    The recent increase in genomic data is revealing an unexpected perspective of gene loss as a pervasive source of genetic variation that can cause adaptive phenotypic diversity. This novel perspective of gene loss is raising new fundamental questions. How relevant has gene loss been in the divergence of phyla? How do genes change from being essential to dispensable and finally to being lost? Is gene loss mostly neutral, or can it be an effective way of adaptation? These questions are addressed, and insights are discussed from genomic studies of gene loss in populations and their relevance in evolutionary biology and biomedicine. PMID:27087500

  12. Human Gene Therapy: Genes without Frontiers?

    ERIC Educational Resources Information Center

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  13. Evolution of gene expression after gene amplification.

    PubMed

    Garcia, Nelson; Zhang, Wei; Wu, Yongrui; Messing, Joachim

    2015-05-01

    We took a rather unique approach to investigate the conservation of gene expression of prolamin storage protein genes across two different subfamilies of the Poaceae. We took advantage of oat plants carrying single maize chromosomes in different cultivars, called oat-maize addition (OMA) lines, which permitted us to determine whether regulation of gene expression was conserved between the two species. We found that γ-zeins are expressed in OMA7.06, which carries maize chromosome 7 even in the absence of the trans-acting maize prolamin-box-binding factor (PBF), which regulates their expression. This is likely because oat PBF can substitute for the function of maize PBF as shown in our transient expression data, using a γ-zein promoter fused to green fluorescent protein (GFP). Despite this conservation, the younger, recently amplified prolamin genes in maize, absent in oat, are not expressed in the corresponding OMAs. However, maize can express the oldest prolamin gene, the wheat high-molecular weight glutenin Dx5 gene, even when maize Pbf is knocked down (through PbfRNAi), and/or another maize transcription factor, Opaque-2 (O2) is knocked out (in maize o2 mutant). Therefore, older genes are conserved in their regulation, whereas younger ones diverged during evolution and eventually acquired a new repertoire of suitable transcriptional activators. PMID:25912045

  14. Evolution of Gene Expression after Gene Amplification

    PubMed Central

    Garcia, Nelson; Zhang, Wei; Wu, Yongrui; Messing, Joachim

    2015-01-01

    We took a rather unique approach to investigate the conservation of gene expression of prolamin storage protein genes across two different subfamilies of the Poaceae. We took advantage of oat plants carrying single maize chromosomes in different cultivars, called oat–maize addition (OMA) lines, which permitted us to determine whether regulation of gene expression was conserved between the two species. We found that γ-zeins are expressed in OMA7.06, which carries maize chromosome 7 even in the absence of the trans-acting maize prolamin-box-binding factor (PBF), which regulates their expression. This is likely because oat PBF can substitute for the function of maize PBF as shown in our transient expression data, using a γ-zein promoter fused to green fluorescent protein (GFP). Despite this conservation, the younger, recently amplified prolamin genes in maize, absent in oat, are not expressed in the corresponding OMAs. However, maize can express the oldest prolamin gene, the wheat high-molecular weight glutenin Dx5 gene, even when maize Pbf is knocked down (through PbfRNAi), and/or another maize transcription factor, Opaque-2 (O2) is knocked out (in maize o2 mutant). Therefore, older genes are conserved in their regulation, whereas younger ones diverged during evolution and eventually acquired a new repertoire of suitable transcriptional activators. PMID:25912045

  15. Reading and Generalist Genes

    ERIC Educational Resources Information Center

    Haworth, Claire M. A.; Meaburn, Emma L.; Harlaar, Nicole; Plomin, Robert

    2007-01-01

    Twin-study research suggests that many (but not all) of the same genes contribute to genetic influence on diverse learning abilities and disabilities, a hypothesis called "generalist genes". This generalist genes hypothesis was tested using a set of 10 DNA markers (single nucleotide polymorphisms [SNPs]) found to be associated with early reading…

  16. Accepting Foreign Genes.

    PubMed

    Boto, Luis

    2016-05-01

    Three recent papers underline the importance of the host genomic background in allowing the stable maintenance of horizontally acquired genes. These studies suggest that post-transfer changes in both host genome and acquired genes contribute to the stable integration of foreign genes. PMID:27075565

  17. [Imprinted genes in plants].

    PubMed

    Zhang, Li-Geng; Yang, Ruo-Fei; Fu, Feng-Ling; Li, Wan-Chen

    2010-12-01

    The expression of imprinted genes is regulated by epigenetic mechanism. In plant endosperm, the allele of imprinted genes is expressed in a pattern of parent-of-origin-dependent. The expression of imprinted genes plays essential roles in the development of embryos and their annexe structures, as well as seed size, reproductive barriers and apomixis. Along with the progress of plant epigenetic research, the exploration of imprinted genes is becoming hotspot in epigenetic research. This review focused on the parental conflict theory about the origin of imprinted genes, and the latest research advances in expression regulation mechanism of plant imprinted genes, using the examples of the important imprinted genes MEA, FIS2, FWA, MPC, and PHE1 in Arabidopsis, and FIEI and FIE2 in maize. PMID:21513148

  18. Retrieval with gene queries

    PubMed Central

    Sehgal, Aditya K; Srinivasan, Padmini

    2006-01-01

    Background Accuracy of document retrieval from MEDLINE for gene queries is crucially important for many applications in bioinformatics. We explore five information retrieval-based methods to rank documents retrieved by PubMed gene queries for the human genome. The aim is to rank relevant documents higher in the retrieved list. We address the special challenges faced due to ambiguity in gene nomenclature: gene terms that refer to multiple genes, gene terms that are also English words, and gene terms that have other biological meanings. Results Our two baseline ranking strategies are quite similar in performance. Two of our three LocusLink-based strategies offer significant improvements. These methods work very well even when there is ambiguity in the gene terms. Our best ranking strategy offers significant improvements on three different kinds of ambiguities over our two baseline strategies (improvements range from 15.9% to 17.7% and 11.7% to 13.3% depending on the baseline). For most genes the best ranking query is one that is built from the LocusLink (now Entrez Gene) summary and product information along with the gene names and aliases. For others, the gene names and aliases suffice. We also present an approach that successfully predicts, for a given gene, which of these two ranking queries is more appropriate. Conclusion We explore the effect of different post-retrieval strategies on the ranking of documents returned by PubMed for human gene queries. We have successfully applied some of these strategies to improve the ranking of relevant documents in the retrieved sets. This holds true even when various kinds of ambiguity are encountered. We feel that it would be very useful to apply strategies like ours on PubMed search results as these are not ordered by relevance in any way. This is especially so for queries that retrieve a large number of documents. PMID:16630348

  19. Do housekeeping genes exist?

    PubMed

    Zhang, Yijuan; Li, Ding; Sun, Bingyun

    2015-01-01

    The searching of human housekeeping (HK) genes has been a long quest since the emergence of transcriptomics, and is instrumental for us to understand the structure of genome and the fundamentals of biological processes. The resolved genes are frequently used in evolution studies and as normalization standards in quantitative gene-expression analysis. Within the past 20 years, more than a dozen HK-gene studies have been conducted, yet none of them sampled human tissues completely. We believe an integration of these results will help remove false positive genes owing to the inadequate sampling. Surprisingly, we only find one common gene across 15 examined HK-gene datasets comprising 187 different tissue and cell types. Our subsequent analyses suggest that it might not be appropriate to rigidly define HK genes as expressed in all tissue types that have diverse developmental, physiological, and pathological states. It might be beneficial to use more robustly identified HK functions for filtering criteria, in which the representing genes can be a subset of genome. These genes are not necessarily the same, and perhaps need not to be the same, everywhere in our body. PMID:25970694

  20. Towards Consensus Gene Ages.

    PubMed

    Liebeskind, Benjamin J; McWhite, Claire D; Marcotte, Edward M

    2016-01-01

    Correctly estimating the age of a gene or gene family is important for a variety of fields, including molecular evolution, comparative genomics, and phylogenetics, and increasingly for systems biology and disease genetics. However, most studies use only a point estimate of a gene's age, neglecting the substantial uncertainty involved in this estimation. Here, we characterize this uncertainty by investigating the effect of algorithm choice on gene-age inference and calculate consensus gene ages with attendant error distributions for a variety of model eukaryotes. We use 13 orthology inference algorithms to create gene-age datasets and then characterize the error around each age-call on a per-gene and per-algorithm basis. Systematic error was found to be a large factor in estimating gene age, suggesting that simple consensus algorithms are not enough to give a reliable point estimate. We also found that different sources of error can affect downstream analyses, such as gene ontology enrichment. Our consensus gene-age datasets, with associated error terms, are made fully available at so that researchers can propagate this uncertainty through their analyses (geneages.org). PMID:27259914

  1. Do Housekeeping Genes Exist?

    PubMed Central

    Sun, Bingyun

    2015-01-01

    The searching of human housekeeping (HK) genes has been a long quest since the emergence of transcriptomics, and is instrumental for us to understand the structure of genome and the fundamentals of biological processes. The resolved genes are frequently used in evolution studies and as normalization standards in quantitative gene-expression analysis. Within the past 20 years, more than a dozen HK-gene studies have been conducted, yet none of them sampled human tissues completely. We believe an integration of these results will help remove false positive genes owing to the inadequate sampling. Surprisingly, we only find one common gene across 15 examined HK-gene datasets comprising 187 different tissue and cell types. Our subsequent analyses suggest that it might not be appropriate to rigidly define HK genes as expressed in all tissue types that have diverse developmental, physiological, and pathological states. It might be beneficial to use more robustly identified HK functions for filtering criteria, in which the representing genes can be a subset of genome. These genes are not necessarily the same, and perhaps need not to be the same, everywhere in our body. PMID:25970694

  2. The gap gene network

    PubMed Central

    2010-01-01

    Gap genes are involved in segment determination during the early development of the fruit fly Drosophila melanogaster as well as in other insects. This review attempts to synthesize the current knowledge of the gap gene network through a comprehensive survey of the experimental literature. I focus on genetic and molecular evidence, which provides us with an almost-complete picture of the regulatory interactions responsible for trunk gap gene expression. I discuss the regulatory mechanisms involved, and highlight the remaining ambiguities and gaps in the evidence. This is followed by a brief discussion of molecular regulatory mechanisms for transcriptional regulation, as well as precision and size-regulation provided by the system. Finally, I discuss evidence on the evolution of gap gene expression from species other than Drosophila. My survey concludes that studies of the gap gene system continue to reveal interesting and important new insights into the role of gene regulatory networks in development and evolution. PMID:20927566

  3. Metastasis Suppressor Genes

    PubMed Central

    Yan, Jinchun; Yang, Qin; Huang, Qihong

    2014-01-01

    Metastasis is a major cause of cancer mortality. Metastasis is a complex process that requires the regulation of both metastasis-promoting and metastasis suppressor genes. The discovery of metastasis suppressor genes contributes significantly to our understanding of metastasis mechanisms and provides prognostic markers and therapeutic targets in clinical cancer management. In this review, we summarize the methods that have been used to identify metastasis suppressors and the potential clinical impact of these genes. PMID:23348381

  4. History of gene therapy.

    PubMed

    Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

    2013-08-10

    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality. PMID:23618815

  5. Towards Consensus Gene Ages

    PubMed Central

    Liebeskind, Benjamin J.; McWhite, Claire D.; Marcotte, Edward M.

    2016-01-01

    Correctly estimating the age of a gene or gene family is important for a variety of fields, including molecular evolution, comparative genomics, and phylogenetics, and increasingly for systems biology and disease genetics. However, most studies use only a point estimate of a gene’s age, neglecting the substantial uncertainty involved in this estimation. Here, we characterize this uncertainty by investigating the effect of algorithm choice on gene-age inference and calculate consensus gene ages with attendant error distributions for a variety of model eukaryotes. We use 13 orthology inference algorithms to create gene-age datasets and then characterize the error around each age-call on a per-gene and per-algorithm basis. Systematic error was found to be a large factor in estimating gene age, suggesting that simple consensus algorithms are not enough to give a reliable point estimate. We also found that different sources of error can affect downstream analyses, such as gene ontology enrichment. Our consensus gene-age datasets, with associated error terms, are made fully available at so that researchers can propagate this uncertainty through their analyses (geneages.org). PMID:27259914

  6. [The gene or genes of allergic asthma?].

    PubMed

    Demoly, P; Bousquet, J; Godard, P; Michel, F B

    1993-05-15

    Asthma is a multifactorial disease in which the hereditary component has been demonstrated by familial and identical twin studies. Allergy is important in the aetiology of asthma and is characterized by a hyperreaction to allergens triggering predominantly the immunoglobulines E. The levels of these antibodies are found to be elevated even in non allergic asthmatics. The majority of genetic research in this area is focused on either the genes of the specific immune response or that of the non allergic response. These are the genes of the class II MHC, and the APY gene on chromosome 11q respectively. The modern techniques of molecular genetics and in particular those of inverse genetics have recently contributed to a more comprehensive understanding of this disease. PMID:8316547

  7. GENE EXPRESSION NETWORKS

    EPA Science Inventory

    "Gene expression network" is the term used to describe the interplay, simple or complex, between two or more gene products in performing a specific cellular function. Although the delineation of such networks is complicated by the existence of multiple and subtle types of intera...

  8. Your Genes, Your Choices

    MedlinePlus

    Table of Contents Your Genes, Your Choices describes the Human Genome Project, the science behind it, and the ethical, legal, and social issues that are ... Nothing could be further from the truth. Your Genes, Your Choices points out how the progress of ...

  9. What Is a Gene?

    MedlinePlus

    ... a new kind of medicine — so new that scientists are still doing experiments to see if it works. It uses the technology of genetic engineering to treat a disease caused by a gene that has changed in some way. One method being tested is replacing sick genes with healthy ...

  10. Gene expression networks.

    PubMed

    Thomas, Reuben; Portier, Christopher J

    2013-01-01

    With the advent of microarrays and next-generation biotechnologies, the use of gene expression data has become ubiquitous in biological research. One potential drawback of these data is that they are very rich in features or genes though cost considerations allow for the use of only relatively small sample sizes. A useful way of getting at biologically meaningful interpretations of the environmental or toxicological condition of interest would be to make inferences at the level of a priori defined biochemical pathways or networks of interacting genes or proteins that are known to perform certain biological functions. This chapter describes approaches taken in the literature to make such inferences at the biochemical pathway level. In addition this chapter describes approaches to create hypotheses on genes playing important roles in response to a treatment, using organism level gene coexpression or protein-protein interaction networks. Also, approaches to reverse engineer gene networks or methods that seek to identify novel interactions between genes are described. Given the relatively small sample numbers typically available, these reverse engineering approaches are generally useful in inferring interactions only among a relatively small or an order 10 number of genes. Finally, given the vast amounts of publicly available gene expression data from different sources, this chapter summarizes the important sources of these data and characteristics of these sources or databases. In line with the overall aims of this book of providing practical knowledge to a researcher interested in analyzing gene expression data from a network perspective, the chapter provides convenient publicly accessible tools for performing analyses described, and in addition describe three motivating examples taken from the published literature that illustrate some of the relevant analyses. PMID:23086841

  11. 4. AERIAL VIEW OF GENE WASH RESERVOIR AND GENE CAMP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. AERIAL VIEW OF GENE WASH RESERVOIR AND GENE CAMP LOOKING SOUTHWEST. DAM AND SPILLWAY VISIBLE IN BOTTOM OF PHOTO. - Gene Wash Reservoir & Dam, 2 miles west of Parker Dam, Parker Dam, San Bernardino County, CA

  12. Genes and Social Behavior

    PubMed Central

    Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

    2011-01-01

    What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence behavior; and 2) genetic variation influences brain function and social behavior. We also briefly discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior. PMID:18988841

  13. Terplex Gene Delivery System.

    PubMed

    Kim, Sung Wan

    2005-01-01

    Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16243067

  14. Terplex gene delivery system.

    PubMed

    Kim, Sung Wan

    2005-01-01

    Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene. PMID:16240997

  15. Vaginal gene therapy.

    PubMed

    Rodríguez-Gascón, Alicia; Del Pozo-Rodríguez, Ana; Isla, Arantxazu; Solinís, María Angeles

    2015-09-15

    In the last years, vaginal gene therapy has gained increasing attention mainly for the treatment and control of sexually transmitted infections. DNA delivery has been also suggested to improve reproductive outcomes for women with deficiencies in the female reproductive tract. Although no product has reached clinical phase, preclinical investigations reveal the potential of the vaginal tract as an effective administration route for gene delivery. This review focuses on the main advantages and challenges of vaginal gene therapy, and on the most used nucleic acid delivery systems, including viral and non-viral vectors. Additionally, the advances in the application of vaginal gene therapy for the treatment and/or prevention of infectious diseases such as the human immunodeficiency virus (HIV), the human papillomavirus (HPV) or the herpes simplex virus (HSV) are presented. PMID:26189799

  16. GeneLab

    NASA Technical Reports Server (NTRS)

    Berrios, Daniel C.; Thompson, Terri G.

    2015-01-01

    NASA GeneLab is expected to capture and distribute omics data and experimental and process conditions most relevant to research community in their statistical and theoretical analysis of NASAs omics data.

  17. "Bad genes" & criminal responsibility.

    PubMed

    González-Tapia, María Isabel; Obsuth, Ingrid

    2015-01-01

    The genetics of the accused is trying to break into the courts. To date several candidate genes have been put forward and their links to antisocial behavior have been examined and documented with some consistency. In this paper, we focus on the so called "warrior gene", or the low-activity allele of the MAOA gene, which has been most consistently related to human behavior and specifically to violence and antisocial behavior. In preparing this paper we had two objectives. First, to summarize and analyze the current scientific evidence, in order to gain an in depth understanding of the state of the issue and determine whether a dominant line of generally accepted scientific knowledge in this field can be asserted. Second, to derive conclusions and put forward recommendations related to the use of genetic information, specifically the presence of the low-activity genotype of the MAOA gene, in modulation of criminal responsibility in European and US courts. PMID:25708001

  18. Fibrinogen gene regulation.

    PubMed

    Fish, Richard J; Neerman-Arbez, Marguerite

    2012-09-01

    The Aα, Bβ and γ polypeptide chains of fibrinogen are encoded by a three gene cluster on human chromosome four. The fibrinogen genes (FGB-FGA-FGG) are expressed almost exclusively in hepatocytes where their output is coordinated to ensure a sufficient mRNA pool for each chain and maintain an abundant plasma fibrinogen protein level. Fibrinogen gene expression is controlled by the activity of proximal promoters which contain binding sites for hepatocyte transcription factors, including proteins which influence fibrinogen transcription in response to acute-phase inflammatory stimuli. The fibrinogen gene cluster also contains cis regulatory elements; enhancer sequences with liver activities identified by sequence conservation and functional genomics. While the transcriptional control of this gene cluster is fascinating biology, the medical impetus to understand fibrinogen gene regulation stems from the association of cardiovascular disease risk with high level circulating fibrinogen. In the general population this level varies from about 1.5 to 3.5 g/l. This variation between individuals is influenced by genotype, suggesting there are genetic variants contributing to fibrinogen levels which reside in fibrinogen regulatory loci. A complete picture of how fibrinogen genes are regulated will therefore point towards novel sources of regulatory variants. In this review we discuss regulation of the fibrinogen genes from proximal promoters and enhancers, the influence of acute-phase stimulation, post-transcriptional regulation by miRNAs and functional regulatory variants identified in genetic studies. Finally, we discuss the fibrinogen locus in light of recent advances in understanding chromosomal architecture and suggest future directions for researching the mechanisms that control fibrinogen expression. PMID:22836683

  19. Gene therapy in epilepsy

    PubMed Central

    Riban, Véronique; Fitzsimons, Helen L.; During, Matthew J.

    2009-01-01

    SUMMARY Results from animal models suggest gene therapy is a promising new approach for the treatment of epilepsy. Several candidate genes such as neuropeptide Y and galanin have been demonstrated in preclinical studies to have a positive effect on seizure activity. For a successful gene therapy-based treatment, efficient delivery of a transgene to target neurons is also essential. To this end, advances have been made in the areas of cell transplantation and in the development of recombinant viral vectors for gene delivery. Recombinant adeno-associated viral (rAAV) vectors in particular show promise for gene therapy of neurological disorders due to their neuronal tropism, lack of toxicity, and stable persistence in neurons, which results in robust, long-term expression of the transgene. rAAV vectors have been recently used in phase I clinical trials of Parkinson’s disease with an excellent safety profile. Prior to commencement of phase I trials for gene therapy of epilepsy, further preclinical studies are ongoing including evaluation of the therapeutic benefit in chronicmodels of epileptogenesis, as well as assessment of safety intoxicological studies. PMID:18717707

  20. Evidence for homosexuality gene

    SciTech Connect

    Pool, R.

    1993-07-16

    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  1. 5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP PLANT IS AT CENTER WITH ADMINISTRATIVE COMPLEX IN FOREGROUND AND RESIDENTIAL AREA BEYOND PLANT. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

  2. Identification of four soybean reference genes for gene expression normalization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gene expression analysis requires the use of reference genes stably expressed independently of specific tissues or environmental conditions. Housekeeping genes (e.g., actin, tubulin, ribosomal, polyubiquitin and elongation factor 1-alpha) are commonly used as reference genes with the assumption tha...

  3. Prospects for gene therapy.

    PubMed

    Ali, Robin R

    2004-01-01

    Inherited retinal disease, which includes conditions such as retinitis pigmentosa (RP), affects about 1/3000 of the population in the Western world. It is characterized by gradual loss of vision and results from mutations in any one of 60 or so different genes. There are currently no effective treatments, but many of the genes have now been identified and their functions elucidated, providing a major impetus to develop gene-based treatments. Many of the disease genes are photoreceptor- or retinal pigment epithelium (RPE) cell specific. Since adeno-associated viral (AAV) vectors can be used for efficient gene transfer to these two cell types, we are developing AAV-mediated gene therapy approaches for inherited retinal degeneration using animal models that have defects in these cells. The retinal degeneration slow (rds or Prph2Rd2/Rd) mouse, a model of recessive RP, lacks a functional gene encoding peripherin 2, which is a photoreceptor-specific protein required for the formation of outer segment discs. We have previously demonstrated restoration of photoreceptor ultrastructure and function by AAV-mediated gene transfer of peripherin 2. We have now extended our assessment to central visual neuronal responses in order to show an improvement of central visual function. The Royal College of Surgeons (RCS) rat, provides another model of recessive RP. Here the defect is due to a defect in Mertk, a gene that is expressed in the RPE and encodes a receptor tyrosine kinase that is thought to be involved in the recognition and binding of outer segment debris. The gene defect results in the inability of the RPE to phagocytose the shed outer segments from photoreceptor cells. The resulting accumulation of debris between the RPE and the neuroretina leads to progressive loss of photoreceptor cells. AAV-mediated delivery of Mertk to the RPE results in reduction of debris indicating that the phagocytosing function of the RPE is restored and delays the degeneration of the

  4. Classification of genes based on gene expression analysis

    NASA Astrophysics Data System (ADS)

    Angelova, M.; Myers, C.; Faith, J.

    2008-05-01

    Systems biology and bioinformatics are now major fields for productive research. DNA microarrays and other array technologies and genome sequencing have advanced to the point that it is now possible to monitor gene expression on a genomic scale. Gene expression analysis is discussed and some important clustering techniques are considered. The patterns identified in the data suggest similarities in the gene behavior, which provides useful information for the gene functionalities. We discuss measures for investigating the homogeneity of gene expression data in order to optimize the clustering process. We contribute to the knowledge of functional roles and regulation of E. coli genes by proposing a classification of these genes based on consistently correlated genes in expression data and similarities of gene expression patterns. A new visualization tool for targeted projection pursuit and dimensionality reduction of gene expression data is demonstrated.

  5. Classification of genes based on gene expression analysis

    SciTech Connect

    Angelova, M. Myers, C. Faith, J.

    2008-05-15

    Systems biology and bioinformatics are now major fields for productive research. DNA microarrays and other array technologies and genome sequencing have advanced to the point that it is now possible to monitor gene expression on a genomic scale. Gene expression analysis is discussed and some important clustering techniques are considered. The patterns identified in the data suggest similarities in the gene behavior, which provides useful information for the gene functionalities. We discuss measures for investigating the homogeneity of gene expression data in order to optimize the clustering process. We contribute to the knowledge of functional roles and regulation of E. coli genes by proposing a classification of these genes based on consistently correlated genes in expression data and similarities of gene expression patterns. A new visualization tool for targeted projection pursuit and dimensionality reduction of gene expression data is demonstrated.

  6. GeneCards Version 3: the human gene integrator.

    PubMed

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-01-01

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73,000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards' unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene's functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite. Database

  7. How old is my gene?

    PubMed Central

    Capra, John A.; Stolzer, Maureen; Durand, Dannie; Pollard, Katherine S.

    2013-01-01

    Gene functions, interactions, disease associations, and ecological distributions are all correlated with gene age. However, it is challenging to estimate the intricate series of evolutionary events leading to a modern day gene and then reduce this history to a single age estimate. Focusing on eukaryotic gene families, we introduce a framework in which to compare current strategies for quantifying gene age, discuss key differences between these methods, and highlight several common problems. We argue that genes with complex evolutionary histories do not have a single well-defined age. As a result, care must be taken to articulate the goals and assumptions of any analysis that uses gene age estimates. Recent algorithmic advances offer the promise of gene age estimates that are fast, accurate, and consistent across gene families. This will enable a shift to integrated genome-wide analyses of all events in gene evolutionary histories in the near future. PMID:23915718

  8. LQTS gene LOVD database.

    PubMed

    Zhang, Tao; Moss, Arthur; Cong, Peikuan; Pan, Min; Chang, Bingxi; Zheng, Liangrong; Fang, Quan; Zareba, Wojciech; Robinson, Jennifer; Lin, Changsong; Li, Zhongxiang; Wei, Junfang; Zeng, Qiang; Qi, Ming

    2010-11-01

    The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders that predisposes young individuals to ventricular arrhythmias and sudden death. LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion channels (KCNQ1, KCNH2,SCN5A, KCNE1, and KCNE2). Many other genes involved in LQTS have been described recently(KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and CAV3). We created an online database(http://www.genomed.org/LOVD/introduction.html) that provides information on variants in LQTS-associated genes. As of February 2010, the database contains 1738 unique variants in 12 genes. A total of 950 variants are considered pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292 have no known pathogenicity. In addition to these mutations collected from published literature, we also submitted information on gene variants, including one possible novel pathogenic mutation in the KCNH2 splice site found in ten Chinese families with documented arrhythmias. The remote user is able to search the data and is encouraged to submit new mutations into the database. The LQTS database will become a powerful tool for both researchers and clinicians. PMID:20809527

  9. Saporin suicide gene therapy.

    PubMed

    Zarovni, Natasa; Vago, Riccardo; Fabbrini, Maria Serena

    2009-01-01

    New genes useful in suicide gene therapy are those encoding toxins such as plant ribosome-inactivating proteins (RIPs), which can irreversibly block protein synthesis, triggering apoptotic cell death. Plasmids expressing a cytosolic saporin (SAP) gene from common soapwort (Saponaria officinalis) are generated by placing the region encoding the mature plant toxin under the control of strong viral promoters and may be placed under tumor-specific promoters. The ability of the resulting constructs to inhibit protein synthesis is tested in cultured tumor cells co-transfected with a luciferase reporter gene. SAP expression driven by the cytomegalovirus (CMV) promoter (pCI-SAP) demonstrates that only 10 ng ofplasmid DNA per 1.6 x 10(4) B16 melanoma cells drastically reduces luciferase reporter activity to 18% of that in control cells (1). Direct intratumoral injections are performed in an aggressive melanoma model. B16 melanoma-bearing mice injected with pCI-SAP complexed with lipofectamine or N-(2,3-dioleoyloxy-1-propyl) trimethylammonium methyl sulfate (DOTAP) show a noteworthy attenuation in tumor growth, and this effect is significantly augmented by repeated administrations of the DNA complexes. Here, we describe in detail this cost-effective and safe suicide gene approach. PMID:19565907

  10. Hox genes and evolution

    PubMed Central

    Hrycaj, Steven M.; Wellik, Deneen M.

    2016-01-01

    Hox proteins are a deeply conserved group of transcription factors originally defined for their critical roles in governing segmental identity along the antero-posterior (AP) axis in Drosophila. Over the last 30 years, numerous data generated in evolutionarily diverse taxa have clearly shown that changes in the expression patterns of these genes are closely associated with the regionalization of the AP axis, suggesting that Hox genes have played a critical role in the evolution of novel body plans within Bilateria. Despite this deep functional conservation and the importance of these genes in AP patterning, key questions remain regarding many aspects of Hox biology. In this commentary, we highlight recent reports that have provided novel insight into the origins of the mammalian Hox cluster, the role of Hox genes in the generation of a limbless body plan, and a novel putative mechanism in which Hox genes may encode specificity along the AP axis. Although the data discussed here offer a fresh perspective, it is clear that there is still much to learn about Hox biology and the roles it has played in the evolution of the Bilaterian body plan. PMID:27239281

  11. Engineered Gene Circuits

    NASA Astrophysics Data System (ADS)

    Hasty, Jeff

    2003-03-01

    Uncovering the structure and function of gene regulatory networks has become one of the central challenges of the post-genomic era. Theoretical models of protein-DNA feedback loops and gene regulatory networks have long been proposed, and recently, certain qualitative features of such models have been experimentally corroborated. This talk will focus on model and experimental results that demonstrate how a naturally occurring gene network can be used as a ``parts list'' for synthetic network design. The model formulation leads to computational and analytical approaches relevant to nonlinear dynamics and statistical physics, and the utility of such a formulation will be demonstrated through the consideration of specific design criteria for several novel genetic devices. Fluctuations originating from small molecule-number effects will be discussed in the context of model predictions, and the experimental validation of these stochastic effects underscores the importance of internal noise in gene expression. Potential biotech applications will be highlighted within the framework of cellular control schemes. Specifically, the coupling of an oscillating cellular process to a synthetic oscillator will be considered, and the resulting model behavior will be analyzed in the context of synchronization. The underlying methodology highlights the utility of engineering-based methods in the design of synthetic gene regulatory networks.

  12. GeneCards Version 3: the human gene integrator

    PubMed Central

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-01-01

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73 000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards’ unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene’s functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite

  13. FunGene: the functional gene pipeline and repository

    PubMed Central

    Fish, Jordan A.; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C. Titus; Tiedje, James M.; Cole, James R.

    2013-01-01

    Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes. PMID:24101916

  14. Human DNA repair genes.

    PubMed

    Wood, R D; Mitchell, M; Sgouros, J; Lindahl, T

    2001-02-16

    Cellular DNA is subjected to continual attack, both by reactive species inside cells and by environmental agents. Toxic and mutagenic consequences are minimized by distinct pathways of repair, and 130 known human DNA repair genes are described here. Notable features presently include four enzymes that can remove uracil from DNA, seven recombination genes related to RAD51, and many recently discovered DNA polymerases that bypass damage, but only one system to remove the main DNA lesions induced by ultraviolet light. More human DNA repair genes will be found by comparison with model organisms and as common folds in three-dimensional protein structures are determined. Modulation of DNA repair should lead to clinical applications including improvement of radiotherapy and treatment with anticancer drugs and an advanced understanding of the cellular aging process. PMID:11181991

  15. Virus induced gene silencing of Arabidopsis gene homologues in wheat identify genes conferring improved drought tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In a non-model staple crop like wheat, functional validation of potential drought stress responsive genes identified in Arabidopsis could provide gene targets for wheat breeding. Virus induced gene silencing (VIGS) of genes of interest can overcome the inherent problems of polyploidy and limited tra...

  16. Neighboring Genes Show Correlated Evolution in Gene Expression

    PubMed Central

    Ghanbarian, Avazeh T.; Hurst, Laurence D.

    2015-01-01

    When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (<100 kb) but extends much further. Sex-specific expression change is also genomically clustered. As genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

  17. Prokaryotic gene prediction using GeneMark and GeneMark.hmm.

    PubMed

    Borodovsky, Mark; Mills, Ryan; Besemer, John; Lomsadze, Alex

    2003-05-01

    In this unit, the GeneMark and GeneMark.hmm programs are presented as two different methods for the in silico prediction of genes in prokaryotes. GeneMark can be used for whole genome analysis as well as for the local analysis of a particular gene and its surrounding regions. GeneMark.hmm makes use of Hidden Markov models to find the transition points (boundaries) between protein coding states and noncoding states and can be efficiently used for larger genome sequences. These methods can be used in conjunction with each other for a higher sensitivity of gene detection. PMID:18428700

  18. Genes and Vocal Learning

    PubMed Central

    White, Stephanie A.

    2009-01-01

    Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in primates, rodents and birds suggests that FoxP2 and other language-related genes are interactors in the neuromolecular networks that underlie subsystems of language, such symbolic understanding, vocal learning and theory of mind. The whole picture will only come together through comparative and integrative study into how the human language singularity evolved. PMID:19913899

  19. XLMR genes: Update 1994

    SciTech Connect

    Neri, G.; Chiurazzi, P.; Arena, J.F.; Lubs, H.A.

    1994-07-15

    We provide a comprehensive list of all known forms of X-linked mental retardation. It comprises 127 entries, subdivided into 5 categories (syndromes, dominant disorders, and nonspecific mental retardation). Map location of 69 putative loci demonstrates several overlaps, which will only be resolved by more refined mapping or cloning of the respective genes. The ultimate goal of identifying all the genes on the X chromosome whose mutations cause mental retardation will require a concerted effort between clinical and molecular investigators. 74 refs., 2 figs., 5 tabs.

  20. The gene tree delusion.

    PubMed

    Springer, Mark S; Gatesy, John

    2016-01-01

    Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are

  1. Gene therapy: progress and predictions

    PubMed Central

    Collins, Mary; Thrasher, Adrian

    2015-01-01

    The first clinical gene delivery, which involved insertion of a marker gene into lymphocytes from cancer patients, was published 25 years ago. In this review, we describe progress since then in gene therapy. Patients with some inherited single-gene defects can now be treated with their own bone marrow stem cells that have been engineered with a viral vector carrying the missing gene. Patients with inherited retinopathies and haemophilia B can also be treated by local or systemic injection of viral vectors. There are also a number of promising gene therapy approaches for cancer and infectious disease. We predict that the next 25 years will see improvements in safety, efficacy and manufacture of gene delivery vectors and introduction of gene-editing technologies to the clinic. Gene delivery may also prove a cost-effective method for the delivery of biological medicines. PMID:26702034

  2. Multidimensional gene search with Genehopper

    PubMed Central

    Munz, Matthias; Tönnies, Sascha; Balke, Wolf-Tilo; Simon, Eric

    2015-01-01

    The high abundance of genetic information enables researchers to gain new insights from the comparison of human genes according to their similarities. However, existing tools that allow the exploration of such gene-to-gene relationships, apply each similarity independently. To make use of multidimensional scoring, we developed a new search engine named Genehopper. It can handle two query types: (i) the typical use case starts with a term-to-gene search, i.e. an optimized full-text search for an anchor gene of interest. The web-interface can handle one or more terms including gene symbols and identifiers of Ensembl, UniProt, EntrezGene and RefSeq. (ii) When the anchor gene is defined, the user can explore its neighborhood by a gene-to-gene search as the weighted sum of nine normalized gene similarities based on sequence homology, protein domains, mRNA expression profiles, Gene Ontology Annotation, gene symbols and other features. Each weight can be adjusted by the user, allowing flexible customization of the gene search. All implemented similarities have a low pairwise correlation (max r2 = 0.4) implying a low linear dependency, i.e. any change in a single weight has an effect on the ranking. Thus, we treated them as separate dimensions in the search space. Genehopper is freely available at http://genehopper.ifis.cs.tu-bs.de. PMID:25990726

  3. Multidimensional gene search with Genehopper.

    PubMed

    Munz, Matthias; Tönnies, Sascha; Balke, Wolf-Tilo; Simon, Eric

    2015-07-01

    The high abundance of genetic information enables researchers to gain new insights from the comparison of human genes according to their similarities. However, existing tools that allow the exploration of such gene-to-gene relationships, apply each similarity independently. To make use of multidimensional scoring, we developed a new search engine named Genehopper. It can handle two query types: (i) the typical use case starts with a term-to-gene search, i.e. an optimized full-text search for an anchor gene of interest. The web-interface can handle one or more terms including gene symbols and identifiers of Ensembl, UniProt, EntrezGene and RefSeq. (ii) When the anchor gene is defined, the user can explore its neighborhood by a gene-to-gene search as the weighted sum of nine normalized gene similarities based on sequence homology, protein domains, mRNA expression profiles, Gene Ontology Annotation, gene symbols and other features. Each weight can be adjusted by the user, allowing flexible customization of the gene search. All implemented similarities have a low pairwise correlation (max r(2) = 0.4) implying a low linear dependency, i.e. any change in a single weight has an effect on the ranking. Thus, we treated them as separate dimensions in the search space. Genehopper is freely available at http://genehopper.ifis.cs.tu-bs.de. PMID:25990726

  4. Gene therapy in pancreatic cancer

    PubMed Central

    Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

    2014-01-01

    Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC. PMID:25309069

  5. Association Between a Prognostic Gene Signature and Functional Gene Sets

    PubMed Central

    Hummel, Manuela; Metzeler, Klaus H.; Buske, Christian; Bohlander, Stefan K.; Mansmann, Ulrich

    2008-01-01

    Background The development of expression-based gene signatures for predicting prognosis or class membership is a popular and challenging task. Besides their stringent validation, signatures need a functional interpretation and must be placed in a biological context. Popular tools such as Gene Set Enrichment have drawbacks because they are restricted to annotated genes and are unable to capture the information hidden in the signature’s non-annotated genes. Methodology We propose concepts to relate a signature with functional gene sets like pathways or Gene Ontology categories. The connection between single signature genes and a specific pathway is explored by hierarchical variable selection and gene association networks. The risk score derived from an individual patient’s signature is related to expression patterns of pathways and Gene Ontology categories. Global tests are useful for these tasks, and they adjust for other factors. GlobalAncova is used to explore the effect on gene expression in specific functional groups from the interaction of the score and selected mutations in the patient’s genome. Results We apply the proposed methods to an expression data set and a corresponding gene signature for predicting survival in Acute Myeloid Leukemia (AML). The example demonstrates strong relations between the signature and cancer-related pathways. The signature-based risk score was found to be associated with development-related biological processes. Conclusions Many authors interpret the functional aspects of a gene signature by linking signature genes to pathways or relevant functional gene groups. The method of gene set enrichment is preferred to annotating signature genes to specific Gene Ontology categories. The strategies proposed in this paper go beyond the restriction of annotation and deepen the insights into the biological mechanisms reflected in the information given by a signature. PMID:19812786

  6. Old genes experience stronger translational selection than young genes.

    PubMed

    Yin, Hongyan; Ma, Lina; Wang, Guangyu; Li, Mengwei; Zhang, Zhang

    2016-09-15

    Selection on synonymous codon usage for translation efficiency and/or accuracy has been identified as a widespread mechanism in many living organisms. However, it remains unknown whether translational selection associates closely with gene age and acts differentially on genes with different evolutionary ages. To address this issue, here we investigate the strength of translational selection acting on different aged genes in human. Our results show that old genes present stronger translational selection than young genes, demonstrating that translational selection correlates positively with gene age. We further explore the difference of translational selection in duplicates vs. singletons and in housekeeping vs. tissue-specific genes. We find that translational selection acts comparably in old singletons and old duplicates and stronger translational selection in old genes is contributed primarily by housekeeping genes. For young genes, contrastingly, singletons experience stronger translational selection than duplicates, presumably due to redundant function of duplicated genes during their early evolutionary stage. Taken together, our results indicate that translational selection acting on a gene would not be constant during all stages of evolution, associating closely with gene age. PMID:27259662

  7. Genes2FANs: connecting genes through functional association networks

    PubMed Central

    2012-01-01

    Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs), researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI) network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our finding that disease genes in

  8. Resistance gene capture.

    PubMed

    Rowe-Magnus, D A; Mazel, D

    1999-10-01

    Integrons are the primary mechanism for antibiotic-resistance gene capture and dissemination among Gram-negative bacteria. The recent finding of super-integron structures in the genomes of several bacterial species has expanded their role in genome evolution and suggests that they are the source of mobile multi-resistant integrons. PMID:10508722

  9. Naming genes beyond Caenorhabditis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The nomenclature of genes in Caenorhabditis elegans is based on long-standing, successful guidelines established in the late 1970s. Over time these guidelines have matured into a comprehensive, systematic nomenclature that is easy to apply, descriptive and therefore highly informative. Recently, a f...

  10. Gene stacking by recombinases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Efficient methods of stacking genes into plant genomes are needed to expedite transfer of multigenic traits into diverse crops grown in a variety of environments. Over two decades of research has identified several site-specific recombinases that carry out efficient cis and trans recombination betw...

  11. Gene Manipulation In Cereals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aluminum, the most abundant metal on earth, is detrimental to plant growth and agricultural production. There are about 2.5 billion hectares of acid soils high in aluminum around the world. Molecular markers linked to aluminum tolerance gene complexes in rye would be of value in marker-mediated ge...

  12. Ultrasound mediated gene transfection

    NASA Astrophysics Data System (ADS)

    Williamson, Rene G.; Apfel, Robert E.; Brandsma, Janet L.

    2002-05-01

    Gene therapy is a promising modality for the treatment of a variety of human diseases both inherited and acquired, such as cystic fibrosis and cancer. The lack of an effective, safe method for the delivery of foreign genes into the cells, a process known as transfection, limits this effort. Ultrasound mediated gene transfection is an attractive method for gene delivery since it is a noninvasive technique, does not introduce any viral particles into the host and can offer very good temporal and spatial control. Previous investigators have shown that sonication increases transfection efficiency with and without ultrasound contrast agents. The mechanism is believed to be via a cavitation process where collapsing bubble nuclei permeabilize the cell membrane leading to increased DNA transfer. The research is focused on the use of pulsed wave high frequency focused ultrasound to transfect DNA into mammalian cells in vitro and in vivo. A better understanding of the mechanism behind the transfection process is also sought. A summary of some in vitro results to date will be presented, which includes the design of a sonication chamber that allows us to model the in vivo case more accurately.

  13. Genes and Vocal Learning

    ERIC Educational Resources Information Center

    White, Stephanie A.

    2010-01-01

    Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in…

  14. Entrez Gene: gene-centered information at NCBI.

    PubMed

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2007-01-01

    Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is provided via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programing utilities (E-Utilities), and for bulk transfer by ftp. PMID:17148475

  15. Magnetic nanoparticles: Applications in gene delivery and gene therapy.

    PubMed

    Majidi, Sima; Zeinali Sehrig, Fatemeh; Samiei, Mohammad; Milani, Morteza; Abbasi, Elham; Dadashzadeh, Kianoosh; Akbarzadeh, Abolfazl

    2016-06-01

    Gene therapy is defined as the direct transfer of genetic material to tissues or cells for the treatment of inherited disorders and acquired diseases. For gene delivery, magnetic nanoparticles (MNPs) are typically combined with a delivery platform to encapsulate the gene, and promote cell uptake. Delivery technologies that have been used with MNPs contain polymeric, viral, as well as non-viral platforms. In this review, we focus on targeted gene delivery using MNPs. PMID:25727710

  16. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    PubMed

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

  17. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis

    PubMed Central

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

  18. Dominance from the perspective of gene-gene and gene-chemical interactions.

    PubMed

    Gladki, Arkadiusz; Zielenkiewicz, Piotr; Kaczanowski, Szymon

    2016-02-01

    In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe. PMID:26613610

  19. Avirulence Genes in Cereal Powdery Mildews: The Gene-for-Gene Hypothesis 2.0

    PubMed Central

    Bourras, Salim; McNally, Kaitlin E.; Müller, Marion C.; Wicker, Thomas; Keller, Beat

    2016-01-01

    The gene-for-gene hypothesis states that for each gene controlling resistance in the host, there is a corresponding, specific gene controlling avirulence in the pathogen. Allelic series of the cereal mildew resistance genes Pm3 and Mla provide an excellent system for genetic and molecular analysis of resistance specificity. Despite this opportunity for molecular research, avirulence genes in mildews remain underexplored. Earlier work in barley powdery mildew (B.g. hordei) has shown that the reaction to some Mla resistance alleles is controlled by multiple genes. Similarly, several genes are involved in the specific interaction of wheat mildew (B.g. tritici) with the Pm3 allelic series. We found that two mildew genes control avirulence on Pm3f: one gene is involved in recognition by the resistance protein as demonstrated by functional studies in wheat and the heterologous host Nicotiana benthamiana. A second gene is a suppressor, and resistance is only observed in mildew genotypes combining the inactive suppressor and the recognized Avr. We propose that such suppressor/avirulence gene combinations provide the basis of specificity in mildews. Depending on the particular gene combinations in a mildew race, different genes will be genetically identified as the “avirulence” gene. Additionally, the observation of two LINE retrotransposon-encoded avirulence genes in B.g. hordei further suggests that the control of avirulence in mildew is more complex than a canonical gene-for-gene interaction. To fully understand the mildew–cereal interactions, more knowledge on avirulence determinants is needed and we propose ways how this can be achieved based on recent advances in the field. PMID:26973683

  20. Gene prediction and gene classes in Arabidopsis thaliana.

    PubMed

    Mathé, C; Déhais, P; Pavy, N; Rombauts, S; Van Montagu, M; Rouzé, P

    2000-03-31

    Gene prediction methods for eukaryotic genomes still are not fully satisfying. One way to improve gene prediction accuracy, proven to be relevant for prokaryotes, is to consider more than one model of genes. Thus, we used our classification of Arabidopsis thaliana genes in two classes (CU(1) and CU(2)), previously delineated according to statistical features, in the GeneMark gene identification program. For each gene class, as well as for the two classes combined, a Markov model was developed (respectively, GM-CU(1), GM-CU(2) and GM-all) and then used on a test set of 168 genes to compare their respective efficiency. We concluded from this analysis that GM-CU(1) is more sensitive than GM-CU(2) which seems to be more specific to a gene type. Besides, GM-all does not give better results than GM-CU(1) and combining results from GM-CU(1) and GM-CU(2) greatly improve prediction efficiency in comparison with predictions made with GM-all only. Thus, this work confirms the necessity to consider more than one gene model for gene prediction in eukaryotic genomes, and to look for gene classes in order to build these models. PMID:10751690

  1. GENE METHYLATION CHANGES IN TUMOR SUPPRESSOR GENES INDUCED BY ARSENIC

    EPA Science Inventory

    The choice of a dose-response model used for extrapolation can be influenced by knowledge of mechanism of action. We have already showed that arsenic affects methylation of the human p53 gene promoter. Evidence that genes other than the p53 tumor suppressor gene are affected woul...

  2. Eukaryotic gene prediction using GeneMark.hmm-E and GeneMark-ES.

    PubMed

    Borodovsky, Mark; Lomsadze, Alex

    2011-09-01

    This unit describes how to use the gene-finding programs GeneMark.hmm-E and GeneMark-ES for finding protein-coding genes in the genomic DNA of eukaryotic organisms. These bioinformatics tools have been demonstrated to have state-of-the-art accuracy for many fungal, plant, and animal genomes, and have frequently been used for gene annotation in novel genomic sequences. An additional advantage of GeneMark-ES is that the problem of algorithm parameterization is solved automatically, with parameters estimated by iterative self-training (unsupervised training). PMID:21901742

  3. SOX genes: architects of development.

    PubMed Central

    Prior, H. M.; Walter, M. A.

    1996-01-01

    Development in higher organisms involves complex genetic regulation at the molecular level. The emerging picture of development control includes several families of master regulatory genes which can affect the expression of down-stream target genes in developmental cascade pathways. One new family of such development regulators is the SOX gene family. The SOX genes are named for a shared motif called the SRY box a region homologous to the DNA-binding domain of SRY, the mammalian sex determining gene. Like SRY, SOX genes play important roles in chordate development. At least a dozen human SOX genes have been identified and partially characterized (Tables 1 and 2). Mutations in SOX9 have recently been linked to campomelic dysplasia and autosomal sex reversal, and other SOX genes may also be associated with human disease. Images FIG. 1 FIG. 2 PMID:8827711

  4. Chapter 15: Disease Gene Prioritization

    PubMed Central

    Bromberg, Yana

    2013-01-01

    Disease-causing aberrations in the normal function of a gene define that gene as a disease gene. Proving a causal link between a gene and a disease experimentally is expensive and time-consuming. Comprehensive prioritization of candidate genes prior to experimental testing drastically reduces the associated costs. Computational gene prioritization is based on various pieces of correlative evidence that associate each gene with the given disease and suggest possible causal links. A fair amount of this evidence comes from high-throughput experimentation. Thus, well-developed methods are necessary to reliably deal with the quantity of information at hand. Existing gene prioritization techniques already significantly improve the outcomes of targeted experimental studies. Faster and more reliable techniques that account for novel data types are necessary for the development of new diagnostics, treatments, and cure for many diseases. PMID:23633938

  5. On atavisms and atavistic genes.

    PubMed

    Cantú, J M; Ruiz, C

    1985-01-01

    The authors propose the term atavistic to designate a gene producing an ancestral phenotype (atavism). Several examples are presented, and the possible origin of atavistic genes, as well as their pathological implications discussed. PMID:3879145

  6. Gene Therapy for Lung Cancer.

    PubMed

    Lara-Guerra, Humberto; Roth, Jack A

    2016-01-01

    Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible. To overcome these difficulties, various gene therapy strategies have been adopted, including immune stimulation, transfer of suicide genes, inhibition of driver oncogenes, replacement of tumor-suppressor genes that could mediate apoptosis or anti-angiogenesis, and transfer of genes that enhance conventional treatments such as radiotherapy and chemotherapy. Some of these strategies have been tested successfully in non-small-cell lung cancer patients and the results of laboratory studies and clinical trials are reviewed herein. PMID:27481008

  7. Gene Testing for Hereditary Ataxia

    MedlinePlus

    ... have a family history of ataxia, but diagnostic tests for known ataxia genes cannot explain the ataxia in their family. In recent years, scientists have developed technologies to sequence thousands of genes at the same ...

  8. Gene expression technology

    SciTech Connect

    Goeddel, D.V. )

    1990-01-01

    The articles in this volume were assemble to enable the reader to design effective strategies for the expression of cloned genes and cDNAs. More than a compilation of papers describing the multitude of techniques now available for expressing cloned genes, this volume provides a manual that should prove useful for solving the majority of expression problems one likely to encounter. The four major expression systems commonly available to most investigators are stressed: Escherichia coli, Bacillus subtilis, yeast, and mammalian cells. Each of these system has its advantages and disadvantages, details of which are found in Chapter 1 and the strategic overviews for the four major sections of the volume. The papers in each of these sections provide many suggestions on how to proceed if initial expression levels are not sufficient.

  9. Gene therapy in keratoconus

    PubMed Central

    Farjadnia, Mahgol; Naderan, Mohammad; Mohammadpour, Mehrdad

    2015-01-01

    Keratoconus (KC) is the most common ectasia of the cornea and is a common reason for corneal transplant. Therapeutic strategies that can arrest the progression of this disease and modify the underlying pathogenesis are getting more and more popularity among scientists. Cumulating data represent strong evidence of a genetic role in the pathogenesis of KC. Different loci have been identified, and certain mutations have also been mapped for this disease. Moreover, Biophysical properties of the cornea create an appropriate candidate of this tissue for gene therapy. Immune privilege, transparency and ex vivo stability are among these properties. Recent advantage in vectors, besides the ability to modulate the corneal milieu for accepting the target gene for a longer period and fruitful translation, make a big hope for stupendous results reasonable. PMID:25709266

  10. Graphene based gene transfection

    NASA Astrophysics Data System (ADS)

    Feng, Liangzhu; Zhang, Shuai; Liu, Zhuang

    2011-03-01

    Graphene as a star in materials research has been attracting tremendous attentions in the past few years in various fields including biomedicine. In this work, for the first time we successfully use graphene as a non-toxic nano-vehicle for efficient gene transfection. Graphene oxide (GO) is bound with cationic polymers, polyethyleneimine (PEI) with two different molecular weights at 1.2 kDa and 10 kDa, forming GO-PEI-1.2k and GO-PEG-10k complexes, respectively, both of which are stable in physiological solutions. Cellular toxicity tests reveal that our GO-PEI-10k complex exhibits significantly reduced toxicity to the treated cells compared to the bare PEI-10k polymer. The positively charged GO-PEI complexes are able to further bind with plasmid DNA (pDNA) for intracellular transfection of the enhanced green fluorescence protein (EGFP) gene in HeLa cells. While EGFP transfection with PEI-1.2k appears to be ineffective, high EGFP expression is observed using the corresponding GO-PEI-1.2k as the transfection agent. On the other hand, GO-PEI-10k shows similar EGFP transfection efficiency but lower toxicity compared with PEI-10k. Our results suggest graphene to be a novel gene delivery nano-vector with low cytotoxicity and high transfection efficiency, promising for future applications in non-viral based gene therapy.Graphene as a star in materials research has been attracting tremendous attentions in the past few years in various fields including biomedicine. In this work, for the first time we successfully use graphene as a non-toxic nano-vehicle for efficient gene transfection. Graphene oxide (GO) is bound with cationic polymers, polyethyleneimine (PEI) with two different molecular weights at 1.2 kDa and 10 kDa, forming GO-PEI-1.2k and GO-PEG-10k complexes, respectively, both of which are stable in physiological solutions. Cellular toxicity tests reveal that our GO-PEI-10k complex exhibits significantly reduced toxicity to the treated cells compared to the bare PEI

  11. Brains, Genes and Primates

    PubMed Central

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

    2015-01-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  12. Eukaryotic gene prediction using GeneMark.hmm.

    PubMed

    Borodovsky, Mark; Lomsadze, Alex; Ivanov, Nikolai; Mills, Ryan

    2003-05-01

    In this unit, eukaryotic GeneMark.hmm is presented as a method for detecting genes in eukaryotic DNA sequences. The eukaryotic GeneMark.hmm uses Markov models of protein coding and noncoding sequences, as well as positional nucleotide frequency matrices for prediction of the translational start, translational termination and splice sites. All these models along with length distributions of exons, introns and intergenic regions are integrated into one Hidden Markov model. The unit describes running the program over the Internet and locally on a Unix machine. It also discusses GeneMarkS EV, which can be used to detect genes in eukaryotic viruses. PMID:18428701

  13. Time ordering of gene coexpression.

    PubMed

    Leng, Xiaoyan; Müller, Hans-Georg

    2006-10-01

    Temporal microarray gene expression profiles allow characterization of gene function through time dynamics of gene coexpression within the same genetic pathway. In this paper, we define and estimate a global time shift characteristic for each gene via least squares, inferred from pairwise curve alignments. These time shift characteristics of individual genes reflect a time ordering that is derived from ob- served temporal gene expression profiles. Once these time shift characteristics are obtained for each gene, they can be entered into further analyses, such as clustering. We illustrate the proposed methodology using Drosophila embryonic development and yeast cell-cycle gene expression profiles, as well as simulations. Feasibility is demonstrated through the successful recovery of time ordering. Estimated time shifts for Drosophila maternal and zygotic genes provide excellent discrimination between these two categories and confirm known genetic pathways through the time order of gene expression. The application to yeast cell-cycle data establishes a natural time order of genes that is in line with cell-cycle phases. The method does not require periodicity of gene expression profiles. Asymptotic justifications are also provided. PMID:16495429

  14. Independent Gene Discovery and Testing

    ERIC Educational Resources Information Center

    Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

    2010-01-01

    A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

  15. Gene Porter Bridwell

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Gene Porter Bridwell served as the director of the Marshall Space Flight Center from January 6, 1994 until February 3, 1996, when he retired from NASA after thirty-four years service. Bridwell, a Marshall employee since 1962, had been Marshall's Space Shuttle Projects Office Director and Space Station Redesign Team deputy manager. Under Bridwell, Marshall worked to develop its role as a Center of Excellence for propulsion and for providing access to space.

  16. Genes and athletes.

    PubMed

    Patel, Dilip R; Greydanus, Donald E

    2002-06-01

    Genetics plays an important role in determining characteristics desired for success in a given sport. Advances in biotechnology pose interesting and perplexing dilemmas for athletes, parents, health care providers, and society at large. Gene therapy holds great prospects for disease prevention and treatment. The same techniques also can be misused for genetic manipulation to enhance athletic prowess. This chapter reviews selective aspects of genotype influence on sport performance, uses and misuses of genetic technology, and ethical as well as legal dilemmas. PMID:11986034

  17. nanosheets for gene therapy

    NASA Astrophysics Data System (ADS)

    Kou, Zhongyang; Wang, Xin; Yuan, Renshun; Chen, Huabin; Zhi, Qiaoming; Gao, Ling; Wang, Bin; Guo, Zhaoji; Xue, Xiaofeng; Cao, Wei; Guo, Liang

    2014-10-01

    A new class of two-dimensional (2D) nanomaterial, transition metal dichalcogenides (TMDCs) such as MoS2, MoSe2, WS2, and WSe2 which have fantastic physical and chemical properties, has drawn tremendous attention in different fields recently. Herein, we for the first time take advantage of the great potential of MoS2 with well-engineered surface as a novel type of 2D nanocarriers for gene delivery and therapy of cancer. In our system, positively charged MoS2-PEG-PEI is synthesized with lipoic acid-modified polyethylene glycol (LA-PEG) and branched polyethylenimine (PEI). The amino end of positively charged nanomaterials can bind to the negatively charged small interfering RNA (siRNA). After detection of physical and chemical characteristics of the nanomaterial, cell toxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polo-like kinase 1 (PLK1) was investigated as a well-known oncogene, which was a critical regulator of cell cycle transmission at multiple levels. Through knockdown of PLK1 with siRNA carried by novel nanovector, qPCR and Western blot were used to measure the interfering efficiency; apoptosis assay was used to detect the transfection effect of PLK1. All results showed that the novel nanocarrier revealed good biocompatibility, reduced cytotoxicity, as well as high gene-carrying ability without serum interference, thus would have great potential for gene delivery and therapy.

  18. Extracting gene-gene interactions through curve fitting.

    PubMed

    Das, Ranajit; Mitra, Sushmita; Murthy, C A

    2012-12-01

    This paper presents a simple and novel curve fitting approach for generating simple gene regulatory subnetworks from time series gene expression data. Microarray experiments simultaneously generate massive data sets and help immensely in the large-scale study of gene expression patterns. Initial biclustering reduces the search space in the high-dimensional microarray data. The least-squares error between fitting of gene pairs is minimized to extract a set of gene-gene interactions, involving transcriptional regulation of genes. The higher error values are eliminated to retain only the strong interacting gene pairs in the resultant gene regulatory subnetwork. Next the algorithm is extended to a generalized framework to enhance its capability. The methodology takes care of the higher-order dependencies involving multiple genes co-regulating a single gene, while eliminating the need for user-defined parameters. It has been applied to the time-series Yeast data, and the experimental results biologically validated using standard databases and literature. PMID:22997274

  19. Gene variants associated with age at menopause are also associated with polycystic ovary syndrome, gonadotrophins and ovarian volume

    PubMed Central

    Saxena, R.; Bjonnes, A.C.; Georgopoulos, N.A.; Koika, V.; Panidis, D.; Welt, C.K.

    2015-01-01

    STUDY QUESTION Is there a relationship between the genetic risk for polycystic ovary syndrome (PCOS) and genetic variants that influence timing of menopause? SUMMARY ANSWER The genetic risk score, which sums the contribution of variants at all menopause loci, was associated with PCOS. WHAT IS ALREADY KNOWN Ovarian parameters and anti-Mullerian hormone levels suggest that women with PCOS should have a later age at menopause. STUDY DESIGN, SIZE, DURATION The study was a case–control examination of genetic variants associated with age at menopause in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston recruited from 2003 to 2012. Replication was performed in women from Greece (cases, n = 884 and controls, n = 311). PARTICIPANTS/MATERIALS, SETTINGS, METHODS PCOS was defined by the National Institutes of Health criteria in Boston and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. Allele frequencies for variants previously associated with age at menopause were examined in PCOS cases and controls, along with the relationship to quantitative traits. MAIN RESULTS AND ROLE OF CHANCE The variant rs11668344-G was associated with decreased risk of PCOS (odds ratio: 0.77 [0.59–0.93]; P = 0.004). There was a strong relationship between the late menopause allele rs12294104-T and increased LH levels (β ± SE; 0.26 ± 0.06; P = 5.2 × 10−5) and the LH:FSH ratio (0.28 ± 0.06; P = 2.7 × 10−6). The minor allele at rs10852344-T was associated with smaller ovarian volume (−0.16 ± 0.05; P = 0.0012). A genetic risk score calculated from 16 independent variants associated with age at menopause was also associated with PCOS (P < 0.02), LH and the LH:FSH ratio (both P < 0.05). LIMITATIONS, REASONS FOR CAUTION The variant rs11668344 was not associated

  20. From SNPs to Genes: Disease Association at the Gene Level

    PubMed Central

    Lehne, Benjamin; Lewis, Cathryn M.; Schlitt, Thomas

    2011-01-01

    Interpreting Genome-Wide Association Studies (GWAS) at a gene level is an important step towards understanding the molecular processes that lead to disease. In order to incorporate prior biological knowledge such as pathways and protein interactions in the analysis of GWAS data it is necessary to derive one measure of association for each gene. We compare three different methods to obtain gene-wide test statistics from Single Nucleotide Polymorphism (SNP) based association data: choosing the test statistic from the most significant SNP; the mean test statistics of all SNPs; and the mean of the top quartile of all test statistics. We demonstrate that the gene-wide test statistics can be controlled for the number of SNPs within each gene and show that all three methods perform considerably better than expected by chance at identifying genes with confirmed associations. By applying each method to GWAS data for Crohn's Disease and Type 1 Diabetes we identified new potential disease genes. PMID:21738570

  1. Advances in Gene Delivery Systems

    PubMed Central

    Kamimura, Kenya; Suda, Takeshi; Zhang, Guisheng; Liu, Dexi

    2011-01-01

    The transfer of genes into cells, both in vitro and in vivo, is critical for studying gene function and conducting gene therapy. Methods that utilize viral and nonviral vectors, as well as physical approaches, have been explored. Viral vector-mediated gene transfer employs replication-deficient viruses such as retro-virus, adenovirus, adeno-associated virus and herpes simplex virus. A major advantage of viral vectors is their high gene delivery efficiency. The nonviral vectors developed so far include cationic liposomes, cationic polymers, synthetic peptides and naturally occurring compounds. These nonviral vectors appear to be highly effective in gene delivery to cultured cells in vitro but are significantly less effective in vivo. Physical methods utilize mechanical pressure, electric shock or hydrodynamic force to transiently permeate the cell membrane to transfer DNA into target cells. They are simpler than viral- and nonviral-based systems and highly effective for localized gene delivery. The past decade has seen significant efforts to establish the most desirable method for safe, effective and target-specific gene delivery, and good progress has been made. The objectives of this review are to (i) explain the rationale for the design of viral, nonviral and physical methods for gene delivery; (ii) provide a summary on recent advances in gene transfer technology; (iii) discuss advantages and disadvantages of each of the most commonly used gene delivery methods; and (iv) provide future perspectives. PMID:22200988

  2. The Gene Wiki: community intelligence applied to human gene annotation.

    PubMed

    Huss, Jon W; Lindenbaum, Pierre; Martone, Michael; Roberts, Donabel; Pizarro, Angel; Valafar, Faramarz; Hogenesch, John B; Su, Andrew I

    2010-01-01

    Annotating the function of all human genes is a critical, yet formidable, challenge. Current gene annotation efforts focus on centralized curation resources, but it is increasingly clear that this approach does not scale with the rapid growth of the biomedical literature. The Gene Wiki utilizes an alternative and complementary model based on the principle of community intelligence. Directly integrated within the online encyclopedia, Wikipedia, the goal of this effort is to build a gene-specific review article for every gene in the human genome, where each article is collaboratively written, continuously updated and community reviewed. Previously, we described the creation of Gene Wiki 'stubs' for approximately 9000 human genes. Here, we describe ongoing systematic improvements to these articles to increase their utility. Moreover, we retrospectively examine the community usage and improvement of the Gene Wiki, providing evidence of a critical mass of users and editors. Gene Wiki articles are freely accessible within the Wikipedia web site, and additional links and information are available at http://en.wikipedia.org/wiki/Portal:Gene_Wiki. PMID:19755503

  3. Identification of genes and gene products necessary for bacterial bioluminescence.

    PubMed

    Engebrecht, J; Silverman, M

    1984-07-01

    Expression of luminescence in Escherichia coli was recently achieved by cloning genes from the marine bacterium Vibrio fischeri. One DNA fragment on a hybrid plasmid encoded regulatory functions and enzymatic activities necessary for light production. We report the results of a genetic analysis to identify the luminescence genes (lux) that reside on this recombinant plasmid. lux gene mutations were generated by hydroxylamine treatment, and these mutations were ordered on a linear map by complementation in trans with a series of polar transposon insertions on other plasmids. lux genes were defined by complementation of lux gene defects on pairs of plasmids in trans in E. coli. Hybrid plasmids were also used to direct the synthesis of polypeptides in the E. coli minicell system. Seven lux genes and the corresponding gene products were identified from the complementation analysis and the minicell programing experiments. These genes, in the order of their position on a linear map, and the apparent molecular weights of the gene products are luxR (27,000), luxI (25,000), luxC (53,000), luxD (33,000), luxA (40,000), luxB (38,000), and luxE (42,000). From the luminescence phenotypes of E. coli containing mutant plasmids, functions were assigned to these genes: luxA, luxB, luxC, luxD, and luxE encode enzymes for light production and luxR and luxI encode regulatory functions. PMID:6377310

  4. Progress in gene targeting and gene therapy for retinitis pigmentosa

    SciTech Connect

    Farrar, G.J.; Humphries, M.M.; Erven, A.

    1994-09-01

    Previously, we localized disease genes involved in retinitis pigmentosa (RP), an inherited retinal degeneration, close to the rhodopsin and peripherin genes on 3q and 6p. Subsequently, we and others identified mutations in these genes in RP patients. Currently animal models for human retinopathies are being generated using gene targeting by homologous recombination in embryonic stem (ES) cells. Genomic clones for retinal genes including rhodopsin and peripherin have been obtained from a phage library carrying mouse DNA isogenic with the ES cell line (CC1.2). The peripherin clone has been sequenced to establish the genomic structure of the mouse gene. Targeting vectors for rhodopsin and peripherin including a neomycin cassette for positive selection and thymidine kinase genes enabling selection against random intergrants are under construction. Progress in vector construction will be presented. Simultaneously we are developing systems for delivery of gene therapies to retinal tissues utilizing replication-deficient adenovirus (Ad5). Efficacy of infection subsequent to various methods of intraocular injection and with varying viral titers is being assayed using an adenovirus construct containing a CMV promoter LacZ fusion as reporter and the range of tissues infected and the level of duration of LacZ expression monitored. Viral constructs with the LacZ reporter gene under the control of retinal specific promoters such as rhodopsin and IRBP cloned into pXCJL.1 are under construction. An update on developments in photoreceptor cell-directed expression of virally delivered genes will be presented.

  5. Gene Circuit Analysis of the Terminal Gap Gene huckebein

    PubMed Central

    Ashyraliyev, Maksat; Siggens, Ken; Janssens, Hilde; Blom, Joke; Akam, Michael; Jaeger, Johannes

    2009-01-01

    The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network. PMID:19876378

  6. Identifying Gene Interaction Networks

    PubMed Central

    Bebek, Gurkan

    2016-01-01

    In this chapter, we introduce interaction networks by describing how they are generated, where they are stored, and how they are shared. We focus on publicly available interaction networks and describe a simple way of utilizing these resources. As a case study, we used Cytoscape, an open source and easy-to-use network visualization and analysis tool to first gather and visualize a small network. We have analyzed this network’s topological features and have looked at functional enrichment of the network nodes by integrating the gene ontology database. The methods described are applicable to larger networks that can be collected from various resources. PMID:22307715

  7. Gene transfer: transduction.

    PubMed

    Frangipani, Emanuela

    2014-01-01

    Bacteriophages able to propagate on Pseudomonas strains are very common and can be easily isolated from natural environments or lysogenic strains. The development of transducing systems has allowed bacterial geneticists to perform chromosome analyses and mutation mapping. Moreover, these systems have also been proved to be a successful tool for molecular microbiologists to introduce a foreign gene or a mutation into the chromosome of a bacterial cell. This chapter provides a description of the phage methodology illustrated by Adams in 1959 and applicable to strain PAO1 derivatives. PMID:24818891

  8. Genes for sexual behavior.

    PubMed

    Yamamoto, D; Nakano, Y

    1998-05-01

    The mating behavior of Drosophila melanogaster is a stereotyped sequence of fixed action patterns, composed of orientation, tapping, singing, licking, attempted copulation and copulation. Mutations that block a unique aspect of mating behavior were isolated and analyzed at the cellular and molecular levels. The wild-type counterparts of the mutated genes were shown to rescue the phenotypes by their ubiquitous or targeted expression in some of the mutants. This strategy of artificial control of fly behavior opens up an avenue for studies to identify the neural center for individual behavioral actions. PMID:9600058

  9. Computation in gene networks

    NASA Astrophysics Data System (ADS)

    Ben-Hur, Asa; Siegelmann, Hava T.

    2004-03-01

    Genetic regulatory networks have the complex task of controlling all aspects of life. Using a model of gene expression by piecewise linear differential equations we show that this process can be considered as a process of computation. This is demonstrated by showing that this model can simulate memory bounded Turing machines. The simulation is robust with respect to perturbations of the system, an important property for both analog computers and biological systems. Robustness is achieved using a condition that ensures that the model equations, that are generally chaotic, follow a predictable dynamics.

  10. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function.

    PubMed

    Warde-Farley, David; Donaldson, Sylva L; Comes, Ovi; Zuberi, Khalid; Badrawi, Rashad; Chao, Pauline; Franz, Max; Grouios, Chris; Kazi, Farzana; Lopes, Christian Tannus; Maitland, Anson; Mostafavi, Sara; Montojo, Jason; Shao, Quentin; Wright, George; Bader, Gary D; Morris, Quaid

    2010-07-01

    GeneMANIA (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query list, GeneMANIA extends the list with functionally similar genes that it identifies using available genomics and proteomics data. GeneMANIA also reports weights that indicate the predictive value of each selected data set for the query. Six organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Homo sapiens and Saccharomyces cerevisiae) and hundreds of data sets have been collected from GEO, BioGRID, Pathway Commons and I2D, as well as organism-specific functional genomics data sets. Users can select arbitrary subsets of the data sets associated with an organism to perform their analyses and can upload their own data sets to analyze. The GeneMANIA algorithm performs as well or better than other gene function prediction methods on yeast and mouse benchmarks. The high accuracy of the GeneMANIA prediction algorithm, an intuitive user interface and large database make GeneMANIA a useful tool for any biologist. PMID:20576703

  11. Alternative Gene Form Discovery and Candidate Gene Selection from Gene Indexing Projects

    PubMed Central

    Burke, John; Wang, Hui; Hide, Winston; Davison, Daniel B.

    1998-01-01

    Several efforts are under way to partition single-read expressed sequence tag (EST), as well as full-length transcript data, into large-scale gene indices, where transcripts are in common index classes if and only if they share a common progenitor gene. Accurate gene indexing facilitates gene expression studies, as well as inexpensive and early gene sequence discovery through assembly of ESTs that are derived from genes that have not been sequenced by classical methods. We extend, correct, and enhance the information obtained from index groups by splitting index classes into subclasses based on sequence dissimilarity (diversity). Two applications of this are highlighted in this report. First it is shown that our method can ameliorate the damage that artifacts, such as chimerism, inflict on index integrity. Additionally, we demonstrate how the organization imposed by an effective subpartition can greatly increase the sensitivity of gene expression studies by accounting for the existence and tissue- or pathology-specific regulation of novel gene isoforms and polymorphisms. We apply our subpartitioning treatment to the UniGene gene indexing project to measure a marked increase in information quality and abundance (in terms of assembly length and insertion/deletion error) after treatment and demonstrate cases where new levels of information concerning differential expression of alternate gene forms, such as regulated alternative splicing, are discovered. [Tables 2 and 3 can be viewed in their entirety as Online Supplements at http://www.genome.org.] PMID:9521931

  12. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    PubMed Central

    Wold, William S.M.; Toth, Karoly

    2015-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vectors are engineered to replicate preferentially in cancer cells and to destroy cancer cells through the natural process of lytic virus replication. Many clinical trials indicate that replication-defective and replication-competent adenovirus vectors are safe and have therapeutic activity. PMID:24279313

  13. Human AZU-1 gene, variants thereof and expressed gene products

    DOEpatents

    Chen, Huei-Mei; Bissell, Mina

    2004-06-22

    A human AZU-1 gene, mutants, variants and fragments thereof. Protein products encoded by the AZU-1 gene and homologs encoded by the variants of AZU-1 gene acting as tumor suppressors or markers of malignancy progression and tumorigenicity reversion. Identification, isolation and characterization of AZU-1 and AZU-2 genes localized to a tumor suppressive locus at chromosome 10q26, highly expressed in nonmalignant and premalignant cells derived from a human breast tumor progression model. A recombinant full length protein sequences encoded by the AZU-1 gene and nucleotide sequences of AZU-1 and AZU-2 genes and variant and fragments thereof. Monoclonal or polyclonal antibodies specific to AZU-1, AZU-2 encoded protein and to AZU-1, or AZU-2 encoded protein homologs.

  14. Gene function prediction with knowledge from gene ontology.

    PubMed

    Shen, Ying; Zhang, Lin

    2015-01-01

    Gene function prediction is an important problem in bioinformatics. Due to the inherent noise existing in the gene expression data, the attempt to improve the prediction accuracy resorting to new classification techniques is limited. With the emergence of Gene Ontology (GO), extra knowledge about the gene products can be extracted from GO and facilitates solving the gene function prediction problem. In this paper, we propose a new method which utilises GO information to improve the classifiers' performance in gene function prediction. Specifically, our method learns a distance metric under the supervision of the GO knowledge using the distance learning technique. Compared with the traditional distance metrics, the learned one produces a better performance and consequently classification accuracy can be improved. The effectiveness of our proposed method has been corroborated by the extensive experimental results. PMID:26529907

  15. Mullerian inhibiting substance inhibits ovarian cell growth through an Rb-independent mechanism.

    PubMed

    Ha, T U; Segev, D L; Barbie, D; Masiakos, P T; Tran, T T; Dombkowski, D; Glander, M; Clarke, T R; Lorenzo, H K; Donahoe, P K; Maheswaran, S

    2000-11-24

    Müllerian inhibiting substance (MIS), a transforming growth factor-beta family member, causes regression of the Müllerian duct in male embryos. MIS overexpression in transgenic mice ablates the ovary, and MIS inhibits the growth of ovarian cancer cell lines in vitro, suggesting a key role for this hormone in postnatal development of the ovary. This report describes a mechanism for MIS-mediated growth inhibition in both a human epithelial ovarian cancer cell line and a cell line derived from normal ovarian surface epithelium, which is the origin of human epithelial ovarian cancers. MIS-treated cells accumulated in the G(1) phase of the cell cycle and subsequently underwent apoptosis. MIS up-regulated the cyclin-dependent kinase inhibitor p16 through an MIS type II receptor-mediated mechanism and inhibited growth in the absence of detectable or inactive Rb protein. Prolonged treatment with MIS down-regulated the Rb-related protein p130 and increased the Rb family-regulated transcription factor E2F1, overexpression of which inhibited growth. These findings demonstrate that p16 is required for MIS-mediated growth inhibition in ovarian epithelial cells and tumor cells and suggest that up-regulation of E2F1 also plays a role in this process. PMID:10958795

  16. Anti-Mullerian hormone as a predictive endocrine marker for embryo production in the goat.

    PubMed

    Monniaux, Danielle; Baril, Gérard; Laine, Anne-Lyse; Jarrier, Peggy; Poulin, Natividad; Cognié, Juliette; Fabre, Stéphane

    2011-12-01

    Recently, we demonstrated the relationship between anti-Müllerian hormone (AMH) circulating concentrations, ovarian follicles, and embryo production in cattle. However, they have not yet been established in a species with a seasonal breeding activity. Thus, goats were subjected to repeated in vivo embryo production during the breeding season, at the end of the breeding season, and at the end of the anestrus season. Embryo production after FSH treatment was highly repeatable for each goat. Plasma AMH concentrations, measured before the first FSH treatment, were highly correlated with the number of collected, transferable, and freezable embryos, resulting from the three sessions of embryo production. Plasma AMH concentrations transiently decreased after each exogenous FSH treatment, but they showed little change with season, and no relationship was observed between AMH and endogenous FSH concentrations during seasonal transitions. Follicles of 1-5 mm in diameter were the main target of the FSH treatment and were major contributors to circulating AMH concentrations. Granulosa cell AMH expression decreased as the follicle approached terminal development, while the expression of maturation markers (CYP19A1 and FSHR) increased. In conclusion, circulating AMH concentrations can be predictive of the capacity of a donor goat to produce high or low numbers of high-quality embryos. This prediction could be accurately made from a single blood measurement of AMH during either breeding or anestrus seasons. Variability in the number of gonadotropin-responsive follicles of 1-5 mm in diameter between individuals resulted in the differences in circulating AMH concentrations measured between individuals. PMID:21930684

  17. Recanalization of azoospermia due to a Mullerian duct cyst by Nd:YAG laser

    NASA Astrophysics Data System (ADS)

    Gaboardi, Franco; Bozzola, Andrea; Zago, Tiziano; Gulfi, Gildo M.; Galli, Luigi

    1991-07-01

    The Nd:YAG laser treatment of a 32-year-old man affected by azoospermia is presented. Preoperative evaluations showed fructose absence in the ejaculate and transrectal echothomography showed bilateral seminal vesicles dilatation. Before the surgical procedure a transperineal vesicledeferentography echographycally guided was carried out. The exam showed the absence of ejaculatory duct and the presence of cystic dilatation in which both seminal vesicles joined. During the exam a mixture of contrast medium and methylen blue was injected into the seminal vesicles. Later, transurethrally and by means of a sapphire contact tip, a new channel, over the veru montanum, was created by a Nd:YAG laser irradiation (25 Watts/2 seconds). The irradiation was carried out until an efflow of seminal material mixed with blue came out through the new channel. Ten months later the patient has 32.106/ml spermatozoa with good quality of semen analysis.

  18. Mullerian adenosarcoma of the cervix with heterologous elements and sarcomatous overgrowth

    PubMed Central

    Pinto, Karen R.

    2016-01-01

    Cervical adenosarcomas are exceedingly infrequent tumors that occur most often in women of reproductive age. Adenosarcomas comprise benign epithelial elements and malignant stromal elements. The malignant stromal elements can either be homologous, such as fibroblasts or smooth muscle, or heterologous, like cartilage, striated muscle, or bone. We report a case of adenosarcoma of the cervix with heterologous elements and sarcomatous overgrowth in a 38-year-old woman. PMID:26722175

  19. The physiology and clinical utility of anti-Mullerian hormone in women.

    PubMed

    Dewailly, Didier; Andersen, Claus Yding; Balen, Adam; Broekmans, Frank; Dilaver, Nafi; Fanchin, Renato; Griesinger, Georg; Kelsey, Tom W; La Marca, Antonio; Lambalk, Cornelius; Mason, Helen; Nelson, Scott M; Visser, Jenny A; Wallace, W Hamish; Anderson, Richard A

    2014-01-01

    BACKGROUND The measurement of circulating anti-Müllerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS This paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors. RESULTS Physiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future. CONCLUSIONS For the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. An international standard for AMH and improved assay validity are urgently needed to maximize the clinical utility of this very promising biomarker of ovarian function in a large array of clinical situations, both in childhood and adulthood. PMID:24430863

  20. Long-lasting effects of neonatal bisphenol A exposure on the implantation process.

    PubMed

    Varayoud, Jorgelina; Ramos, Jorge G; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2014-01-01

    Successful implantation is the result of complex molecular interactions between the hormonally primed uterus and a mature blastocyst. This very carefully synchronized interplay of hormonal signals and feedback loops is potentially vulnerable to chemicals such as endocrine disruptors that may disrupt endocrine signaling. Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide. This chapter describes the effects of brief postnatal exposure to BPA on female reproductive performance and specifically on the uterine adaptations during the preimplantation period. We propose that an early alteration in Hoxa10 gene expression affects the functional differentiation of the preimplantation uterus as part of an altered endocrine signal transduction pathway. These molecular alterations could explain, at least in part, the adverse effects of BPA on uterine implantation. Exposure to endocrine disruptors, such as BPA, could contribute to the impaired female fertility noted over the past decades. PMID:24388194

  1. Endocrine regulation of HOX genes.

    PubMed

    Daftary, Gaurang S; Taylor, Hugh S

    2006-06-01

    Hox genes have a well-characterized role in embryonic development, where they determine identity along the anteroposterior body axis. Hox genes are expressed not only during embryogenesis but also in the adult, where they are necessary for functional differentiation. Despite the known function of these genes as transcription factors, few regulatory mechanisms that drive Hox expression are known. Recently, several hormones and their cognate receptors have been shown to regulate Hox gene expression and thereby mediate development in the embryo as well as functional differentiation in the adult organism. Estradiol, progesterone, testosterone, retinoic acid, and vitamin D have been shown to regulate Hox gene expression. In the embryo, the endocrine system directs axial Hox gene expression; aberrant Hox gene expression due to exposure to endocrine disruptors contributes to the teratogenicity of these compounds. In the adult, endocrine regulation of Hox genes is necessary to enable such diverse functions as hematopoiesis and reproduction; endocrinopathies can result in dysregulated HOX gene expression affecting physiology. By regulating HOX genes, hormonal signals utilize a conserved mechanism that allows generation of structural and functional diversity in both developing and adult tissues. This review discusses endocrine Hox regulation and its impact on physiology and human pathology. PMID:16632680

  2. Imprinting genes associated with endometriosis

    PubMed Central

    Kobayashi, Hiroshi

    2014-01-01

    Purpose: Much work has been carried out to investigate the genetic and epigenetic basis of endometriosis and proposed that endometriosis has been described as an epigenetic disease. The purpose of this study was to extract the imprinting genes that are associated with endometriosis development. Methods: The information on the imprinting genes can be accessed publicly from a web-based interface at http://www.geneimprint.com/site/genes-by-species. Results: In the current version, the database contains 150 human imprinted genes derived from the literature. We searched gene functions and their roles in particular biological processes or events, such as development and pathogenesis of endometriosis. From the genomic imprinting database, we picked 10 genes that were highly associated with female reproduction; prominent among them were paternally expressed genes (DIRAS3, BMP8B, CYP1B1, ZFAT, IGF2, MIMT1, or MIR296) and maternally expressed genes (DVL1, FGFRL1, or CDKN1C). These imprinted genes may be associated with reproductive biology such as endometriosis, pregnancy loss, decidualization process and preeclampsia. Discussion: This study supports the possibility that aberrant epigenetic dysregulation of specific imprinting genes may contribute to endometriosis predisposition. PMID:26417259

  3. Vectors for cancer gene therapy.

    PubMed

    Zhang, J; Russell, S J

    1996-09-01

    Many viral and non-viral vector systems have now been developed for gene therapy applications. In this article, the pros and cons of these vector systems are discussed in relation to the different cancer gene therapy strategies. The protocols used in cancer gene therapy can be broadly divided into six categories including gene transfer to explanted cells for use as cell-based cancer vaccines; gene transfer to a small number of tumour cells in situ to achieve a vaccine effect; gene transfer to vascular endothelial cells (VECs) lining the blood vessels of the tumour to interfere with tumour angiogenesis; gene transfer to T lymphocytes to enhance their antitumour effector capability; gene transfer to haemopoietic stem cells (HSCs) to enhance their resistance to cytotoxic drugs and gene transfer to a large number of tumour cells in situ to achieve nonimmune tumour reduction with or without bystander effect. Each of the six strategies makes unique demands on the vector system and these are discussed with reference to currently available vectors. Aspects of vector biology that are in need of further development are discussed in some detail. The final section points to the potential use of replicating viruses as delivery vehicles for efficient in vivo gene transfer to disseminated cancers. PMID:9034598

  4. Aberrant Gene Expression in Humans

    PubMed Central

    Yang, Ence; Ji, Guoli; Brinkmeyer-Langford, Candice L.; Cai, James J.

    2015-01-01

    Gene expression as an intermediate molecular phenotype has been a focus of research interest. In particular, studies of expression quantitative trait loci (eQTL) have offered promise for understanding gene regulation through the discovery of genetic variants that explain variation in gene expression levels. Existing eQTL methods are designed for assessing the effects of common variants, but not rare variants. Here, we address the problem by establishing a novel analytical framework for evaluating the effects of rare or private variants on gene expression. Our method starts from the identification of outlier individuals that show markedly different gene expression from the majority of a population, and then reveals the contributions of private SNPs to the aberrant gene expression in these outliers. Using population-scale mRNA sequencing data, we identify outlier individuals using a multivariate approach. We find that outlier individuals are more readily detected with respect to gene sets that include genes involved in cellular regulation and signal transduction, and less likely to be detected with respect to the gene sets with genes involved in metabolic pathways and other fundamental molecular functions. Analysis of polymorphic data suggests that private SNPs of outlier individuals are enriched in the enhancer and promoter regions of corresponding aberrantly-expressed genes, suggesting a specific regulatory role of private SNPs, while the commonly-occurring regulatory genetic variants (i.e., eQTL SNPs) show little evidence of involvement. Additional data suggest that non-genetic factors may also underlie aberrant gene expression. Taken together, our findings advance a novel viewpoint relevant to situations wherein common eQTLs fail to predict gene expression when heritable, rare inter-individual variation exists. The analytical framework we describe, taking into consideration the reality of differential phenotypic robustness, may be valuable for investigating

  5. The Zebrafish Annexin Gene Family

    PubMed Central

    Farber, Steven A.; De Rose, Robert A.; Olson, Eric S.; Halpern, Marnie E.

    2003-01-01

    The Annexins (ANXs) are a family of calcium- and phospholipid-binding proteins that have been implicated in many cellular processes, including channel formation, membrane fusion, vesicle transport, and regulation of phospholipase A2 activity. As a first step toward understanding in vivo function, we have cloned 11 zebrafish anx genes. Four genes (anx1a, anx2a, anx5,and anx11a) were identified by screening a zebrafish cDNA library with a Xenopus anx2 fragment. For these genes, full-length cDNA sequences were used to cluster 212 EST sequences generated by the Zebrafish Genome Resources Project. The EST analysis revealed seven additional anx genes that were subsequently cloned. The genetic map positions of all 11 genes were determined by using a zebrafish radiation hybrid panel. Sequence and syntenic relationships between zebrafish and human genes indicate that the 11 genes represent orthologs of human anx1,2,4,5,6,11,13,and suggest that several zebrafish anx genes resulted from duplications that arose after divergence of the zebrafish and mammalian genomes. Zebrafish anx genes are expressed in a wide range of tissues during embryonic and larval stages. Analysis of the expression patterns of duplicated genes revealed both redundancy and divergence, with the most similar genes having almost identical tissue-specific patterns of expression and with less similar duplicates showing no overlap. The differences in gene expression of recently duplicated anx genes could explain why highly related paralogs were maintained in the genome and did not rapidly become pseudogenes. PMID:12799347

  6. Gene-gene interaction between tuberculosis candidate genes in a South African population.

    PubMed

    de Wit, Erika; van der Merwe, Lize; van Helden, Paul D; Hoal, Eileen G

    2011-02-01

    In a complex disease such as tuberculosis (TB) it is increasingly evident that gene-gene interactions play a far more important role in an individual's susceptibility to develop the disease than single polymorphisms on their own, as one gene can enhance or hinder the expression of another gene. Gene-gene interaction analysis is a new approach to elucidate susceptibility to TB. The possibility of gene-gene interactions was assessed, focusing on 11 polymorphisms in nine genes (DC-SIGN, IFN-γ, IFNGR1, IL-8, IL-1Ra, MBL, NRAMP1, RANTES, and SP-D) that have been associated with TB, some repeatedly. An optimal model, which best describes and predicts TB case-control status, was constructed. Significant interactions were detected between eight pairs of variants. The models fitted the observed data extremely well, with p < 0.0001 for all eight models. A highly significant interaction was detected between INFGR1 and NRAMP1, which is not surprising because macrophage activation is greatly enhanced by IFN-γ and IFN-γ response elements that are present in the human NRAMP1 promoter region, providing further evidence for their interaction. This study enabled us to test the theory that disease outcome may be due to interaction of several gene effects. With eight instances of statistically significant gene-gene interactions, the importance of epistasis is clearly identifiable in this study. Methods for studying gene-gene interactions are based on a multilocus and multigene approach, consistent with the nature of complex-trait diseases, and may provide the paradigm for future genetic studies of TB. PMID:20799037

  7. Identifying Driver Genes in Cancer by Triangulating Gene Expression, Gene Location, and Survival Data

    PubMed Central

    Rouam, Sigrid; Miller, Lance D; Karuturi, R Krishna Murthy

    2014-01-01

    Driver genes are directly responsible for oncogenesis and identifying them is essential in order to fully understand the mechanisms of cancer. However, it is difficult to delineate them from the larger pool of genes that are deregulated in cancer (ie, passenger genes). In order to address this problem, we developed an approach called TRIAngulating Gene Expression (TRIAGE through clinico-genomic intersects). Here, we present a refinement of this approach incorporating a new scoring methodology to identify putative driver genes that are deregulated in cancer. TRIAGE triangulates – or integrates – three levels of information: gene expression, gene location, and patient survival. First, TRIAGE identifies regions of deregulated expression (ie, expression footprints) by deriving a newly established measure called the Local Singular Value Decomposition (LSVD) score for each locus. Driver genes are then distinguished from passenger genes using dual survival analyses. Incorporating measurements of gene expression and weighting them according to the LSVD weight of each tumor, these analyses are performed using the genes located in significant expression footprints. Here, we first use simulated data to characterize the newly established LSVD score. We then present the results of our application of this refined version of TRIAGE to gene expression data from five cancer types. This refined version of TRIAGE not only allowed us to identify known prominent driver genes, such as MMP1, IL8, and COL1A2, but it also led us to identify several novel ones. These results illustrate that TRIAGE complements existing tools, allows for the identification of genes that drive cancer and could perhaps elucidate potential future targets of novel anticancer therapeutics. PMID:25949096

  8. Ancient origins of axial patterning genes: Hox genes and ParaHox genes in the Cnidaria.

    PubMed

    Finnerty, J R; Martindale, M Q

    1999-01-01

    Among the bilaterally symmetrical, triploblastic animals (the Bilateria), a conserved set of developmental regulatory genes are known to function in patterning the anterior-posterior (AP) axis. This set includes the well-studied Hox cluster genes, and the recently described genes of the ParaHox cluster, which is believed to be the evolutionary sister of the Hox cluster (Brooke et al. 1998). The conserved role of these axial patterning genes in animals as diverse as frogs and flies is believed to reflect an underlying homology (i.e., all bilaterians derive from a common ancestor which possessed an AP axis and the developmental mechanisms responsible for patterning the axis). However, the origin and early evolution of Hox genes and ParaHox genes remain obscure. Repeated attempts have been made to reconstruct the early evolution of Hox genes by analyzing data from the triphoblastic animals, the Bilateria (Schubert et al. 1993; Zhang and Nei 1996). A more precise dating of Hox origins has been elusive due to a lack of sufficient information from outgroup taxa such as the phylum Cnidaria (corals, hydras, jellyfishes, and sea anemones). In combination with outgroup taxa, another potential source of information about Hox origins is outgroup genes (e.g., the genes of the ParaHox cluster). In this article, we present cDNA sequences of two Hox-like genes (anthox2 and anthox6) from the sea anemone, Nematostella vectensis. Phylogenetic analysis indicates that anthox2 (= Cnox2) is homologous to the GSX class of ParaHox genes, and anthox6 is homologous to the anterior class of Hox genes. Therefore, the origin of Hox genes and ParaHox genes occurred prior to the evolutionary split between the Cnidaria and the Bilateria and predated the evolution of the anterior-posterior axis of bilaterian animals. Our analysis also suggests that the central Hox class was invented in the bilaterian lineage, subsequent to their split from the Cnidaria. PMID:11324016

  9. Introns in gene evolution.

    PubMed

    Fedorova, Larisa; Fedorov, Alexei

    2003-07-01

    Introns are integral elements of eukaryotic genomes that perform various important functions and actively participate in gene evolution. We review six distinct roles of spliceosomal introns: (1) sources of non-coding RNA; (2) carriers of transcription regulatory elements; (3) actors in alternative and trans-splicing; (4) enhancers of meiotic crossing over within coding sequences; (5) substrates for exon shuffling; and (6) signals for mRNA export from the nucleus and nonsense-mediated decay. We consider transposable capacities of introns and the current state of the long-lasting debate on the 'early-or-late' origin of introns. Cumulative data on known types of contemporary exon shuffling and the estimation of the size of the underlying exon universe are also discussed. We argue that the processes central to introns-early (exon shuffling) and introns-late (intron insertion) theories are entirely compatible. Each has provided insight: the latter through elucidating the transposon capabilities of introns, and the former through understanding the importance of introns in genomic recombination leading to gene rearrangements and evolution. PMID:12868603

  10. Conotoxin Gene Superfamilies

    PubMed Central

    Robinson, Samuel D.; Norton, Raymond S.

    2014-01-01

    Conotoxins are the peptidic components of the venoms of marine cone snails (genus Conus). They are remarkably diverse in terms of structure and function. Unique potency and selectivity profiles for a range of neuronal targets have made several conotoxins valuable as research tools, drug leads and even therapeutics, and has resulted in a concerted and increasing drive to identify and characterise new conotoxins. Conotoxins are translated from mRNA as peptide precursors, and cDNA sequencing is now the primary method for identification of new conotoxin sequences. As a result, gene superfamily, a classification based on precursor signal peptide identity, has become the most convenient method of conotoxin classification. Here we review each of the described conotoxin gene superfamilies, with a focus on the structural and functional diversity present in each. This review is intended to serve as a practical guide to conotoxin superfamilies and to facilitate interpretation of the increasing number of conotoxin precursor sequences being identified by targeted-cDNA sequencing and more recently high-throughput transcriptome sequencing. PMID:25522317

  11. Bacteriophage phiX174: gene A overlaps gene B.

    PubMed Central

    Weisbeek, P J; Borrias, W E; Langeveld, S A; Baas, P D; Van Arkel, G A

    1977-01-01

    The map position of several phiX174 mutations in the genes A and B was determined by marker rescue with DNA fragments produced by the restriction enzymes Hha I, HindII, Hae III, and Alu I. All the gene B mutants were found to be located within gene A. Genetic complementation and analysis of phage-specific protein synthesis show that, under restrictive conditions, nonsense mutants in gene A do not block the synthesis and activity of the B protein and nonsense mutants in gene B do not affect the gene A function. The map position of the COOH-terminal end of gene A was determined using an amber mutant that synthesizes slightly shortened A and A proteins. It is concluded from these experiments that gene A overlaps gene B completely (or almost completely) and that the overlap region can be translated in two ways with different reading frames: one frame for the synthesis of the A and A proteins and another for the synthesis of the B protein. Images PMID:267943

  12. GeneMark.hmm: new solutions for gene finding.

    PubMed

    Lukashin, A V; Borodovsky, M

    1998-02-15

    The number of completely sequenced bacterial genomes has been growing fast. There are computer methods available for finding genes but yet there is a need for more accurate algorithms. The GeneMark. hmm algorithm presented here was designed to improve the gene prediction quality in terms of finding exact gene boundaries. The idea was to embed the GeneMark models into naturally derived hidden Markov model framework with gene boundaries modeled as transitions between hidden states. We also used the specially derived ribosome binding site pattern to refine predictions of translation initiation codons. The algorithm was evaluated on several test sets including 10 complete bacterial genomes. It was shown that the new algorithm is significantly more accurate than GeneMark in exact gene prediction. Interestingly, the high gene finding accuracy was observed even in the case when Markov models of order zero, one and two were used. We present the analysis of false positive and false negative predictions with the caution that these categories are not precisely defined if the public database annotation is used as a control. PMID:9461475

  13. Gene: a gene-centered information resource at NCBI

    PubMed Central

    Brown, Garth R.; Hem, Vichet; Katz, Kenneth S.; Ovetsky, Michael; Wallin, Craig; Ermolaeva, Olga; Tolstoy, Igor; Tatusova, Tatiana; Pruitt, Kim D.; Maglott, Donna R.; Murphy, Terence D.

    2015-01-01

    The National Center for Biotechnology Information's (NCBI) Gene database (www.ncbi.nlm.nih.gov/gene) integrates gene-specific information from multiple data sources. NCBI Reference Sequence (RefSeq) genomes for viruses, prokaryotes and eukaryotes are the primary foundation for Gene records in that they form the critical association between sequence and a tracked gene upon which additional functional and descriptive content is anchored. Additional content is integrated based on the genomic location and RefSeq transcript and protein sequence data. The content of a Gene record represents the integration of curation and automated processing from RefSeq, collaborating model organism databases, consortia such as Gene Ontology, and other databases within NCBI. Records in Gene are assigned unique, tracked integers as identifiers. The content (citations, nomenclature, genomic location, gene products and their attributes, phenotypes, sequences, interactions, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities and Entrez Direct) and for bulk transfer by FTP. PMID:25355515

  14. Gene-targeting pharmaceuticals for single-gene disorders.

    PubMed

    Beaudet, Arthur L; Meng, Linyan

    2016-04-15

    The concept of orphan drugs for treatment of orphan genetic diseases is perceived enthusiastically at present, and this is leading to research investment on the part of governments, disease-specific foundations and industry. This review attempts to survey the potential to use traditional pharmaceuticals as opposed to biopharmaceuticals to treat single-gene disorders. The available strategies include the use of antisense oligonucleotides (ASOs) to alter splicing or knock-down expression of a transcript, siRNAs to knock-down gene expression and drugs for nonsense mutation read-through. There is an approved drug for biallelic knock-down of the APOB gene as treatment for familial hypercholesterolemia. Both ASOs and siRNAs are being explored to knock-down the transthyretin gene to prevent the related form of amyloidosis. The use of ASOs to alter gene-splicing to treat spinal muscular atrophy is in phase 3 clinical trials. Work is progressing on the use of ASOs to activate the normally silent paternal copy of the imprinted UBE3A gene in neurons as a treatment for Angelman syndrome. A gene-activation or gene-specific ramp-up strategy would be generally helpful if such could be developed. There is exciting theoretical potential for converting biopharmaceutical strategies such gene correction and CRISPR-Cas9 editing to a synthetic pharmaceutical approach. PMID:26628634

  15. Immunity-related genes and gene families in Anopheles gambiae.

    PubMed

    Christophides, George K; Zdobnov, Evgeny; Barillas-Mury, Carolina; Birney, Ewan; Blandin, Stephanie; Blass, Claudia; Brey, Paul T; Collins, Frank H; Danielli, Alberto; Dimopoulos, George; Hetru, Charles; Hoa, Ngo T; Hoffmann, Jules A; Kanzok, Stefan M; Letunic, Ivica; Levashina, Elena A; Loukeris, Thanasis G; Lycett, Gareth; Meister, Stephan; Michel, Kristin; Moita, Luis F; Müller, Hans-Michael; Osta, Mike A; Paskewitz, Susan M; Reichhart, Jean-Marc; Rzhetsky, Andrey; Troxler, Laurent; Vernick, Kenneth D; Vlachou, Dina; Volz, Jennifer; von Mering, Christian; Xu, Jiannong; Zheng, Liangbiao; Bork, Peer; Kafatos, Fotis C

    2002-10-01

    We have identified 242 Anopheles gambiae genes from 18 gene families implicated in innate immunity and have detected marked diversification relative to Drosophila melanogaster. Immune-related gene families involved in recognition, signal modulation, and effector systems show a marked deficit of orthologs and excessive gene expansions, possibly reflecting selection pressures from different pathogens encountered in these insects' very different life-styles. In contrast, the multifunctional Toll signal transduction pathway is substantially conserved, presumably because of counterselection for developmental stability. Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire. PMID:12364793

  16. Sexually antagonistic genes: experimental evidence.

    PubMed

    Rice, W R

    1992-06-01

    When selection differs between the sexes, a mutation beneficial to one sex may be harmful to the other (sexually antagonistic). Because the sexes share a common gene pool, selection in one sex can interfere with the other's adaptive evolution. Theory predicts that sexually antagonistic mutations should accumulate in tight linkage with a new sex-determining gene, even when the harm to benefit ratio is high. Genetic markers and artificial selection were used to make a pair of autosomal genes segregate like a new pair of sex-determining genes in a Drosophila melanogaster model system. A 29-generation study provides experimental evidence that sexually antagonistic genes may be common in nature and will accumulate in response to a new sex-determining gene. PMID:1604317

  17. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists. PMID:26069580

  18. Gene targeting with retroviral vectors

    SciTech Connect

    Ellis, J.; Bernstein, A. )

    1989-04-01

    The authors have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. Stable neo gene correction events were selected at a frequency of approximately 1 G418/sup r/ cell per 3 x 10/sup 6/ infected cells. Analysis of the functional neo gene in independent targeted cell clones indicated that unintegrated retroviral linear DNA recombined with the target by gene conversion for variable distances into regions of nonhomology. In addition, transient neo gene correction events which were associated with the complete loss of the chromosomal target sequences were observed. These results demonstrated that retroviral vectors can recombine with homologous chromosomal sequences in rodent and human cells.

  19. The Perils of Gene Patents

    PubMed Central

    Salzberg, SL

    2013-01-01

    I argue here that gene patents, and patented genetic tests based on them, are a very bad idea. First, I discuss whether genes can reasonably be the subject of patents in the first place; I maintain that the answer is no. Second, I explain how gene patents interfere with scientific progress, slowing down the development of new cures and treatments for genetic diseases. PMID:22609909

  20. Symmetry and Stochastic Gene Regulation

    NASA Astrophysics Data System (ADS)

    Ramos, Alexandre F.; Hornos, José E. M.

    2007-09-01

    Lorentz-like noncompact Lie symmetry SO(2,1) is found in a spin-boson stochastic model for gene expression. The invariant of the algebra characterizes the switch decay to equilibrium. The azimuthal eigenvalue describes the affinity between the regulatory protein and the gene operator site. Raising and lowering operators are constructed and their actions increase or decrease the affinity parameter. The classification of the noise regime of the gene arises from the group theoretical numbers.

  1. Combinatorial approaches to gene recognition.

    PubMed

    Roytberg, M A; Astakhova, T V; Gelfand, M S

    1997-01-01

    Recognition of genes via exon assembly approaches leads naturally to the use of dynamic programming. We consider the general graph-theoretical formulation of the exon assembly problem and analyze in detail some specific variants: multicriterial optimization in the case of non-linear gene-scoring functions; context-dependent schemes for scoring exons and related procedures for exon filtering; and highly specific recognition of arbitrary gene segments, oligonucleotide probes and polymerase chain reaction (PCR) primers. PMID:9440930

  2. Serial analysis of gene expression.

    PubMed

    Velculescu, V E; Zhang, L; Vogelstein, B; Kinzler, K W

    1995-10-20

    The characteristics of an organism are determined by the genes expressed within it. A method was developed, called serial analysis of gene expression (SAGE), that allows the quantitative and simultaneous analysis of a large number of transcripts. To demonstrate this strategy, short diagnostic sequence tags were isolated from pancreas, concatenated, and cloned. Manual sequencing of 1000 tags revealed a gene expression pattern characteristic of pancreatic function. New pancreatic transcripts corresponding to novel tags were identified. SAGE should provide a broadly applicable means for the quantitative cataloging and comparison of expressed genes in a variety of normal, developmental, and disease states. PMID:7570003

  3. Gene therapy for Parkinson's disease.

    PubMed

    Lawlor, Patricia A; During, Matthew J

    2004-03-01

    Parkinson's disease (PD) is a debilitating neurodegenerative disorder arising from loss of dopaminergic neurons in the substantia nigra pars compacta and subsequent depletion of striatal dopamine levels, which results in distressing motor symptoms. The current standard pharmacological treatment for PD is direct replacement of dopamine by treatment with its precursor, levodopa (L-dopa). However, this does not significantly alter disease progression and might contribute to the ongoing pathology. Several features of PD make this disease one of the most promising targets for clinical gene therapy of any neurological disease. The confinement of the major pathology to a compact, localised neuronal population and the anatomy of the basal ganglia circuitry mean that global gene transfer is not required and there are well-defined sites for gene transfer. The multifactorial aetiology of idiopathic PD means that it is unlikely any single gene will cure the disease, and as a result at least three separate gene-transfer strategies are currently being pursued: transfer of genes for enzymes involved in dopamine production; transfer of genes for growth factors involved in dopaminergic cell survival and regeneration; and transfer of genes to reset neuronal circuitry by switching cellular phenotype. The merits of these strategies are discussed here, along with remaining hurdles that might impede transfer of gene therapy technology to the clinic as a treatment for PD. PMID:15000692

  4. ERGDB: Estrogen Responsive Genes Database.

    PubMed

    Tang, Suisheng; Han, Hao; Bajic, Vladimir B

    2004-01-01

    ERGDB is an integrated knowledge database dedicated to genes responsive to estrogen. Genes included in ERGDB are those whose expression levels are experimentally proven to be either up-regulated or down-regulated by estrogen. Genes included are identified based on publications from the PubMed database and each record has been manually examined, evaluated and selected for inclusion by biologists. ERGDB aims to be a unified gateway to store, search, retrieve and update information about estrogen responsive genes. Each record contains links to relevant databases, such as GenBank, LocusLink, Refseq, PubMed and ATCC. The unique feature of ERGDB is that it contains information on the dependence of gene reactions on experimental conditions. In addition to basic information about the genes, information for each record includes gene functional description, experimental methods used, tissue or cell type, gene reaction, estrogen exposure time and the summary of putative estrogen response elements if the gene's promoter sequence was available. Through a web interface at http://sdmc.i2r.a-star.edu.sg/ergdb/ cgi-bin/explore.pl users can either browse or query ERGDB. Access is free for academic and non-profit users. PMID:14681475

  5. New genes for boys

    SciTech Connect

    Sinclair, A.H.

    1995-11-01

    Sex is a fascinating topic, particularly at the level of molecular genetics, since it represents a wonderful paradigm for mammalian organ development. Recently, interest in the molecular basis for mammalian sex determination has been heating up as new pieces are added to the jigsaw puzzle of testis development. In mammals, the Y chromosome is male determining and encodes a gene referred to as TDF (testis-determining factor), which induces the indifferent embryonic gonad to develop as a testis. Subsequent male sexual differentiation is largely a consequence of hormonal secretion from the testis. In the absence of the Y chromosome, the testis-determining pathway fails to be initiated, and the embryonic gonad develops as an ovary, resulting in female development. 32 refs.

  6. Taste Receptor Genes

    PubMed Central

    Bachmanov, Alexander A.; Beauchamp, Gary K.

    2009-01-01

    In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity. PMID:17444812

  7. Cardiac Gene Therapy

    PubMed Central

    Chaanine, Antoine H.; Kalman, Jill; Hajjar, Roger J.

    2010-01-01

    Heart failure is a chronic progressive disorder where frequent and recurrent hospitalizations are associated with high mortality and morbidity. The incidence and the prevalence of this disease will increase with the increase in the number of the aging population of the United States. Understanding the molecular pathology and pathophysiology of this disease will uncover novel targets and therapies that can restore the function or attenuate the damage of malfunctioning cardiomyocytes by gene therapy that becomes an interesting and a promising field for the treatment of heart failure as well as other diseases in the future. Of equal importance is developing vectors and delivery methods that can efficiently transduce the majority of the cardiomyocytes, that can offer a long term expression and that can escape the host immune response. Recombinant adeno-associated virus vectors have the potential to become a promising novel therapeutic vehicles for molecular medicine in the future. PMID:21092890

  8. DIFFERENTIAL GENE EXPRESSION OF PUTATIVE VIRULENCE GENES IN Flavobacterium columnare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A shot-gun genomic library of the Flavobacterium columnare ALG-530 virulent strain has been constructed and more than 3,000 clones have been sequenced to date (800 contigs). Based on sequence identity with putative known virulence genes from related species, seven genes were selected for differentia...

  9. Gene Express Inc.

    PubMed

    Saccomanno, Colette F

    2006-07-01

    Gene Express, Inc. is a technology-licensing company and provider of Standardized Reverse Transcription Polymerase Chain Reaction (StaRT-PCR) services. Designed by and for clinical researchers involved in pharmaceutical, biomarker and molecular diagnostic product development, StaRT-PCR is a unique quantitative and standardized multigene expression measurement platform. StaRT-PCR meets all of the performance characteristics defined by the US FDA as required to support regulatory submissions [101,102] , and by the Clinical Laboratory Improvement Act of 1988 (CLIA) as necessary to support diagnostic testing [1] . A standardized mixture of internal standards (SMIS), manufactured in bulk, provides integrated quality control wherein each native template target gene is measured relative to a competitive template internal standard. Bulk production enables the compilation of a comprehensive standardized database from across multiple experiments, across collaborating laboratories and across the entire clinical development lifecycle of a given compound or diagnostic product. For the first time, all these data are able to be directly compared. Access to such a database can dramatically shorten the time from investigational new drug (IND) to new drug application (NDA), or save time and money by hastening a substantiated 'no-go' decision. High-throughput StaRT-PCR is conducted at the company's automated Standardized Expression Measurement (SEM) Center. Currently optimized for detection on a microcapillary electrophoretic platform, StaRT-PCR products also may be analyzed on microarray, high-performance liquid chromatography (HPLC), or matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) platforms. SEM Center services deliver standardized genomic data--data that will accelerate the application of pharmacogenomic technology to new drug and diagnostic test development and facilitate personalized medicine. PMID:16886903

  10. Candidate reference genes for gene expression studies in water lily.

    PubMed

    Luo, Huolin; Chen, Sumei; Wan, Hongjian; Chen, Fadi; Gu, Chunsun; Liu, Zhaolei

    2010-09-01

    The selection of an appropriate reference gene(s) is a prerequisite for the proper interpretation of quantitative Real-Time polymerase chain reaction data. We report the evaluation of eight candidate reference genes across various tissues and treatments in the water lily by the two software packages geNorm and NormFinder. Across all samples, clathrin adaptor complexes medium subunit (AP47) and actin 11 (ACT11) emerged as the most suitable reference genes. Across different tissues, ACT11 and elongation factor 1-alpha (EF1alpha) exhibited a stable expression pattern. ACT11 and AP47 also stably expressed in roots subjected to various treatments, but in the leaves of the same plants the most stably expressed genes were ubiquitin-conjugating enzyme 16 (UBC16) and ACT11. PMID:20452325

  11. Uncovering trends in gene naming

    PubMed Central

    Seringhaus, Michael R; Cayting, Philip D; Gerstein, Mark B

    2008-01-01

    We take stock of current genetic nomenclature and attempt to organize strange and notable gene names. We categorize, for instance, those that involve a naming system transferred from another context (for example, Pavlov’s dogs). We hope this analysis provides clues to better steer gene naming in the future. PMID:18254929

  12. Determining Semantically Related Significant Genes.

    PubMed

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement. PMID:26357049

  13. Candidate gene prioritization with Endeavour.

    PubMed

    Tranchevent, Léon-Charles; Ardeshirdavani, Amin; ElShal, Sarah; Alcaide, Daniel; Aerts, Jan; Auboeuf, Didier; Moreau, Yves

    2016-07-01

    Genomic studies and high-throughput experiments often produce large lists of candidate genes among which only a small fraction are truly relevant to the disease, phenotype or biological process of interest. Gene prioritization tackles this problem by ranking candidate genes by profiling candidates across multiple genomic data sources and integrating this heterogeneous information into a global ranking. We describe an extended version of our gene prioritization method, Endeavour, now available for six species and integrating 75 data sources. The performance (Area Under the Curve) of Endeavour on cross-validation benchmarks using 'gold standard' gene sets varies from 88% (for human phenotypes) to 95% (for worm gene function). In addition, we have also validated our approach using a time-stamped benchmark derived from the Human Phenotype Ontology, which provides a setting close to prospective validation. With this benchmark, using 3854 novel gene-phenotype associations, we observe a performance of 82%. Altogether, our results indicate that this extended version of Endeavour efficiently prioritizes candidate genes. The Endeavour web server is freely available at https://endeavour.esat.kuleuven.be/. PMID:27131783

  14. Using Genes to Guide Prescriptions

    MedlinePlus

    ... Science > Using Genes to Guide Prescriptions Inside Life Science View All Articles | Inside Life Science Home Page Using Genes to Guide Prescriptions By ... to Zoloft: Ways Medicines Work This Inside Life Science article also appears on LiveScience . Learn about related ...

  15. Gene therapy on the move

    PubMed Central

    Kaufmann, Kerstin B; Büning, Hildegard; Galy, Anne; Schambach, Axel; Grez, Manuel

    2013-01-01

    The first gene therapy clinical trials were initiated more than two decades ago. In the early days, gene therapy shared the fate of many experimental medicine approaches and was impeded by the occurrence of severe side effects in a few treated patients. The understanding of the molecular and cellular mechanisms leading to treatment- and/or vector-associated setbacks has resulted in the development of highly sophisticated gene transfer tools with improved safety and therapeutic efficacy. Employing these advanced tools, a series of Phase I/II trials were started in the past few years with excellent clinical results and no side effects reported so far. Moreover, highly efficient gene targeting strategies and site-directed gene editing technologies have been developed and applied clinically. With more than 1900 clinical trials to date, gene therapy has moved from a vision to clinical reality. This review focuses on the application of gene therapy for the correction of inherited diseases, the limitations and drawbacks encountered in some of the early clinical trials and the revival of gene therapy as a powerful treatment option for the correction of monogenic disorders. PMID:24106209

  16. Multifunctional nanorods for gene delivery

    NASA Astrophysics Data System (ADS)

    Salem, Aliasger K.; Searson, Peter C.; Leong, Kam W.

    2003-10-01

    The goal of gene therapy is to introduce foreign genes into somatic cells to supplement defective genes or provide additional biological functions, and can be achieved using either viral or synthetic non-viral delivery systems. Compared with viral vectors, synthetic gene-delivery systems, such as liposomes and polymers, offer several advantages including ease of production and reduced risk of cytotoxicity and immunogenicity, but their use has been limited by the relatively low transfection efficiency. This problem mainly stems from the difficulty in controlling their properties at the nanoscale. Synthetic inorganic gene carriers have received limited attention in the gene-therapy community, the only notable example being gold nanoparticles with surface-immobilized DNA applied to intradermal genetic immunization by particle bombardment. Here we present a non-viral gene-delivery system based on multisegment bimetallic nanorods that can simultaneously bind compacted DNA plasmids and targeting ligands in a spatially defined manner. This approach allows precise control of composition, size and multifunctionality of the gene-delivery system. Transfection experiments performed in vitro and in vivo provide promising results that suggest potential in genetic vaccination applications.

  17. Gene Expression in Oligodendroglial Tumors

    PubMed Central

    Shaw, Elisabeth J.; Haylock, Brian; Husband, David; du Plessis, Daniel; Sibson, D. Ross; Warnke, Peter C.; Walker, Carol

    2010-01-01

    Background: Oligodendroglial tumors with 1p/19q loss are more likely to be chemosensitive and have longer survival than those with intact 1p/19q, but not all respond to chemotherapy, warranting investigation of the biological basis of chemosensitivity. Methods: Gene expression profiling was performed using amplified antisense RNA from 28 oligodendroglial tumors treated with chemotherapy (26 serial stereotactic biopsy, 2 resection). Expression of differentially expressed genes was validated by real-time PCR. Results: Unsupervised hierarchical clustering showed clustering of multiple samples from the same case in 14/17 cases and identified subgroups associated with tumor grade and 1p/19q status. 176 genes were differentially expressed, 164 being associated with 1p/19q loss (86% not on 1p or 19q). 94 genes differed between responders and non-responders to chemotherapy; 12 were not associated with 1p/19q loss. Significant differential expression was confirmed in 11/13 selected genes. Novel genes associated with response to therapy included SSBP2, GFRA1, FAP and RASD1. IQGAP1, INA, TGIF1, NR2F2 and MYCBP were differentially expressed in oligodendroglial tumors with 1p/19q loss. Conclusion: Gene expression profiling using serial stereotactic biopsies indicated greater homogeneity within tumors than between tumors. Genes associated with 1p/19q status or response were identified warranting further elucidation of their role in oligodendroglial tumors. PMID:20966545

  18. From genes to genome biology

    SciTech Connect

    Pennisi, E.

    1996-06-21

    This article describes a change in the approach to mapping genomes, from looking at one gene at a time, to other approaches. Strategies include everything from lab techniques to computer programs designed to analyze whole batches of genes at once. Also included is a update on the work on the human genome.

  19. Method of controlling gene expression

    DOEpatents

    Peters, Norman K.; Frost, John W.; Long, Sharon R.

    1991-12-03

    A method of controlling expression of a DNA segment under the control of a nod gene promoter which comprises administering to a host containing a nod gene promoter an amount sufficient to control expression of the DNA segment of a compound of the formula: ##STR1## in which each R is independently H or OH, is described.

  20. Susceptibility Genes in Thyroid Autoimmunity

    PubMed Central

    Ban, Yoshiyuki; Tomer, Yaron

    2005-01-01

    The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely, these loci interact and their interactions may influence disease phenotype and severity. PMID:15712599

  1. Nonviral Vectors for Gene Delivery

    NASA Astrophysics Data System (ADS)

    Baoum, Abdulgader Ahmed

    2011-12-01

    The development of nonviral vectors for safe and efficient gene delivery has been gaining considerable attention recently. An ideal nonviral vector must protect the gene against degradation by nuclease in the extracellular matrix, internalize the plasma membrane, escape from the endosomal compartment, unpackage the gene at some point and have no detrimental effects. In comparison to viruses, nonviral vectors are relatively easy to synthesize, less immunogenic, low in cost, and have no limitation in the size of a gene that can be delivered. Significant progress has been made in the basic science and applications of various nonviral gene delivery vectors; however, the majority of nonviral approaches are still inefficient and often toxic. To this end, two nonviral gene delivery systems using either biodegradable poly(D,L-lactide- co-glycolide) (PLG) nanoparticles or cell penetrating peptide (CPP) complexes have been designed and studied using A549 human lung epithelial cells. PLG nanoparticles were optimized for gene delivery by varying particle surface chemistry using different coating materials that adsorb to the particle surface during formation. A variety of cationic coating materials were studied and compared to more conventional surfactants used for PLG nanoparticle fabrication. Nanoparticles (˜200 nm) efficiently encapsulated plasmids encoding for luciferase (80-90%) and slowly released the same for two weeks. After a delay, moderate levels of gene expression appeared at day 5 for certain positively charged PLG particles and gene expression was maintained for at least two weeks. In contrast, gene expression mediated by polyethyleneimine (PEI) ended at day 5. PLG particles were also significantly less cytotoxic than PEI suggesting the use of these vehicles for localized, sustained gene delivery to the pulmonary epithelium. On the other hand, a more simple method to synthesize 50-200 nm complexes capable of high transfection efficiency or high gene knockdown was

  2. Fast parsers for Entrez Gene.

    PubMed

    Liu, Mingyi; Grigoriev, Andrei

    2005-07-15

    NCBI completed the transition of its main genome annotation database from Locuslink to Entrez Gene in Spring 2005. However, to this date few parsers exist for the Entrez Gene annotation file. Owing to the widespread use of Locuslink and the popularity of Perl programming language in bioinformatics, a publicly available high performance Entrez Gene parser in Perl is urgently needed. We present four such parsers that were developed using several parsing approaches (Parse::RecDescent, Parse::Yapp, Perl-byacc and Perl 5 regular expressions) and provide the first in-depth comparison of these sophisticated Perl tools. Our fastest parser processes the entire human Entrez Gene annotation file in under 12 min on one Intel Xeon 2.4 GHz CPU and can be of help to the bioinformatics community during and after the transition from Locuslink to Entrez Gene. PMID:15879451

  3. Gene Therapy for Retinal Diseases

    PubMed Central

    Samiy, Nasrollah

    2014-01-01

    Gene therapy has a growing research potential particularly in the field of ophthalmic and retinal diseases owing to three main characteristics of the eye; accessibility in terms of injections and surgical interventions, its immune-privileged status facilitating the accommodation to the antigenicity of a viral vector, and tight blood-ocular barriers which save other organs from unwanted contamination. Gene therapy has tremendous potential for different ocular diseases. In fact, the perspective of gene therapy in the field of eye research does not confine to exclusive monogenic ophthalmic problems and it has the potential to include gene based pharmacotherapies for non-monogenic problems such as age related macular disease and diabetic retinopathy. The present article has focused on how gene transfer into the eye has been developed and used to treat retinal disorders with no available therapy at present. PMID:25709778

  4. The Gene Network Underlying Hypodontia.

    PubMed

    Yin, W; Bian, Z

    2015-07-01

    Mammalian tooth development is a precise and complicated procedure. Several signaling pathways, such as nuclear factor (NF)-κB and WNT, are key regulators of tooth development. Any disturbance of these signaling pathways can potentially affect or block normal tooth development, and presently, there are more than 150 syndromes and 80 genes known to be related to tooth agenesis. Clarifying the interaction and crosstalk among these genes will provide important information regarding the mechanisms underlying missing teeth. In the current review, we summarize recently published findings on genes related to isolated and syndromic tooth agenesis; most of these genes function as positive regulators of cell proliferation or negative regulators of cell differentiation and apoptosis. Furthermore, we explore the corresponding networks involving these genes in addition to their implications for the clinical management of tooth agenesis. We conclude that this requires further study to improve patients' quality of life in the future. PMID:25910507

  5. Immunoglobulin λ Gene Rearrangement Can Precede κ Gene Rearrangement

    DOE PAGESBeta

    Berg, Jörg; Mcdowell, Mindy; Jäck, Hans-Martin; Wabl, Matthias

    1990-01-01

    Imore » mmunoglobulin genes are generated during differentiation of B lymphocytes by joining gene segments. A mouse pre-B cell contains a functional immunoglobulin heavy-chain gene, but no light-chain gene. Although there is only one heavy-chain locus, there are two lightchain loci: κ and λ .It has been reported that κ loci in the germ-line configuration are never (in man) or very rarely (in the mouse) present in cells with functionally rearranged λ -chain genes. Two explanations have been proposed to explain this: (a) the ordered rearrangement theory, which postulates that light-chain gene rearrangement in the pre-B cell is first attempted at the κ locus, and that only upon failure to produce a functional κ chain is there an attempt to rearrange the λ locus; and (b) the stochastic theory, which postulates that rearrangement at the λ locus proceeds at a rate that is intrinsically much slower than that at the κ locus. We show here that λ -chain genes are generated whether or not the κ locus has lost its germ-line arrangement, a result that is compatible only with the stochastic theory.« less

  6. Genes and gene networks implicated in aggression related behaviour.

    PubMed

    Malki, Karim; Pain, Oliver; Du Rietz, Ebba; Tosto, Maria Grazia; Paya-Cano, Jose; Sandnabba, Kenneth N; de Boer, Sietse; Schalkwyk, Leonard C; Sluyter, Frans

    2014-10-01

    Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a global transcriptomic characterization of the prefrontal cortex across all three genetic mouse models of aggression. A systems biology approach has been applied to transcriptomic data across the three pairs of selected inbred mouse strains (Turku Aggressive (TA) and Turku Non-Aggressive (TNA), Short Attack Latency (SAL) and Long Attack Latency (LAL) mice and North Carolina Aggressive (NC900) and North Carolina Non-Aggressive (NC100)), providing novel insight into the neurobiological mechanisms and genetics underlying aggression. First, weighted gene co-expression network analysis (WGCNA) was performed to identify modules of highly correlated genes associated with aggression. Probe sets belonging to gene modules uncovered by WGCNA were carried forward for network analysis using ingenuity pathway analysis (IPA). The RankProd non-parametric algorithm was then used to statistically evaluate expression differences across the genes belonging to modules significantly associated with aggression. IPA uncovered two pathways, involving NF-kB and MAPKs. The secondary RankProd analysis yielded 14 differentially expressed genes, some of which have previously been implicated in pathways associated with aggressive behaviour, such as Adrbk2. The results highlighted plausible candidate genes and gene networks implicated in aggression-related behaviour. PMID:25142712

  7. Gene therapy progress and prospects: gene therapy for diabetes mellitus.

    PubMed

    Yechoor, V; Chan, L

    2005-01-01

    Diabetes mellitus has long been targeted, as yet unsuccessfully, as being curable with gene therapy. The main hurdles have not only been vector-related toxicity but also the lack of physiological regulation of the expressed insulin. Recent advances in understanding the developmental biology of beta-cells and the transcriptional cascade that drives it have enabled both in vivo and ex vivo gene therapy combined with cell therapy to be used in animal models of diabetes with success. The associated developments in the stem cell biology and immunology have opened up further opportunities for gene therapy to be applied to target autoimmune diabetes. PMID:15496957

  8. Genes and equality.

    PubMed

    Farrelly, C

    2004-12-01

    The way people think about equality as a value will influence how they think genetic interventions should be regulated. In this paper the author uses the taxonomy of equality put forth by Derek Parfit and applies this to the issue of genetic interventions. It is argued that telic egalitarianism is untenable and that deontic egalitarianism collapses into prioritarianism. The priority view maintains that it is morally more important to benefit the people who are worse off. Once this precision has been given to the concerns egalitarians have, a number of diverse issues must be considered before determining what the just regulation of genetic interventions would be. Consideration must be given to the current situation of the least advantaged, the fiscal realities behind genetic interventions, the budget constraints on other social programmes egalitarians believe should receive scarce public funds, and the interconnected nature of genetic information. These considerations might lead egalitarians to abandon what they take to be the obvious policy recommendations for them to endorse regarding the regulation of gene therapies and enhancements. PMID:15574450

  9. Genes, Economics, and Happiness *

    PubMed Central

    De Neve, Jan-Emmanuel; Christakis, Nicholas A.; Fowler, James H.; Frey, Bruno S.

    2012-01-01

    We explore the influence of genetic variation on subjective well-being by employing a twin design and genetic association study. In a nationally-representative twin sample, we first show that about 33% of the variation in life satisfaction is explained by genetic variation. Although previous studies have shown that baseline happiness is significantly heritable, little research has considered molecular genetic associations with subjective well-being. We study the relationship between a functional polymorphism on the serotonin transporter gene (5-HTTLPR) and life satisfaction. We initially find that individuals with the longer, transcriptionally more efficient variant of this genotype report greater life satisfaction (n=2,545, p=0.012). However, our replication attempts on independent samples produce mixed results indicating that more work needs to be done to better understand the relationship between this genotype and subjective well-being. This work has implications for how economists think about the determinants of utility, and the extent to which exogenous shocks might affect individual well-being. PMID:24349601

  10. Genes, Economics, and Happiness.

    PubMed

    De Neve, Jan-Emmanuel; Christakis, Nicholas A; Fowler, James H; Frey, Bruno S

    2012-11-01

    We explore the influence of genetic variation on subjective well-being by employing a twin design and genetic association study. In a nationally-representative twin sample, we first show that about 33% of the variation in life satisfaction is explained by genetic variation. Although previous studies have shown that baseline happiness is significantly heritable, little research has considered molecular genetic associations with subjective well-being. We study the relationship between a functional polymorphism on the serotonin transporter gene (5-HTTLPR) and life satisfaction. We initially find that individuals with the longer, transcriptionally more efficient variant of this genotype report greater life satisfaction (n=2,545, p=0.012). However, our replication attempts on independent samples produce mixed results indicating that more work needs to be done to better understand the relationship between this genotype and subjective well-being. This work has implications for how economists think about the determinants of utility, and the extent to which exogenous shocks might affect individual well-being. PMID:24349601