Biomedical subjects

C Fonatsch

Publications and source records attributed to C Fonatsch.

At least 91 records · Page 5Linked to original sources

PubMed1996

Characterization of the continuous cell line HepT1 derived from a human hepatoblastoma.

Hepatoblastoma is the most common malignant pediatric liver tumor. The molecular mechanisms involved in the pathogenesis of hepatoblastoma are unknown. Cell lines can be valuable tools in the study of tumor biology, but only few hepatoblastoma cell lines have been established. We explanted tumor tissue from human hepatoblastomas to generate cell lines. A continuous cell line (HepT1) was established from a human hepatoblastoma with predominant embryonal differentiation. The HepT1 cell line was characterized by immunohistochemistry, electron microscopy, cytogenetics, and molecular genetic analysis. In addition, the cultured cells were xenografted into nude mice and the resulting tumors compared with the original tumor. The cells grew in epithelial clusters, and expressed cytokeratins and alpha-fetoprotein. Injection of HepT1 cells into nude mice gave rise to serially transplantable subcutaneous tumors. The cell line as well as the xenotransplants displayed the phenotypic and genotypic characteristics of the primary tumor. Ultrastructural analysis demonstrated desmosomal junctions and the formation of bile canaliculi. Cytogenetic analysis showed a near tetraploid karyotype with structural and numerical aberrations of chromosomes 1p, 6, 9, 11q, 13q, 15p, and 20 and both single and double minute chromosomes. In PCR-based microsatellite analysis of chromosome arm 11p, a loss of heterozygosity at all informative loci including the WT-1 and IGF2 genes was detected. Intratumoral erythropoiesis, a characteristic feature of hepatoblastomas, was present in the primary tumor as well as in HepT1 xenotransplants. We therefore studied the expression of erythropoietic cytokines in these cells and found both erythropoietin and stem cell factor. The HepT1 cell line displays characteristic cellular and molecular features of hepatoblastoma and we believe it will be a valuable tool for studies on the biology and pathogenesis of hepatoblastoma as well as on the differentiation of hepatocyte progenitor cells.

Animals↗

PubMed1996

De novo AML with dysplastic hematopoiesis: cytogenetic and prognostic significance.

Dysplastic hematopoiesis is the morphological hallmark of myelodysplastic syndromes. Dysplastic features in one or more lineages are also found frequently in bone marrow aspirates from patients with de novo AML and have been associated with an unfavorable prognosis. We asked whether dyshematopoiesis is an independent prognostic factor or an indicator of unrecognized secondary leukemia, identified by characteristic chromosomal abnormalities. Bone marrow aspirates from 102 patients with newly diagnosed AML were analyzed. Morphological analysis was obtained in all patients, flow cytometric analysis in 96 and successful cytogenetic analysis in 65 bone marrow aspirates. Dysgranulopoiesis (DysG) was found in 55, dysmegakaryopoiesis (DysM) in 32 and dyserythropoiesis (DysE) in 23 patients. Decreased side scatter signals of neutrophils in the flow cytometric analysis (DysS) were detected in 32 patients. DysG and DysS showed a highly significant correlation (P = 0.0005). DysG was an adverse negative prognostic factor for remission rate and event-free survival (P = 0.04, P = 0.02). An unfavorable karyotype was associated with a significantly lower chance for event-free survival (P = 0.002). The incidence of an unfavorable karyotype was significantly higher in patients with DysG (P = 0.01), DysM (P = 0.02) and DysS (P = 0.01). In patients with an unfavorable karyotype, dysplasia had no additional prognostic influence, however, in patients with a normal, favorable or prognostically uncertain karyotype DysG remained a predictor of lower remission rate (P = 0.03). We conclude that dysgranulopoiesis, dysmegakaryopoiesis and decreased side scatter signals of neutrophils are indicators of secondary leukemias in bone marrow aspirates from patients with de novo AML.

Bone Marrow↗

PubMed1996

Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor.

The translocation t(8;21)(q22;q22) occurs in 6 to 12 percent of patients with AML, and usually predicts a good response to chemotherapy with a high remission rate and a relatively long median survival. The influence of additional chromosome aberrations on the clinical outcome of patients with t(8;21) is unclear. We analyzed 51 cases of acute myeloid leukemia carrying a translocation t(8;21)(q22;q22); 23 female and 28 male patients. The complete remission rate was 92 percent and median overall survival was 52.4 months. The median overall survival of female patients was significantly worse than of male patients (37.2 months vs not reached, P = 0.025). Additional chromosome aberrations were detected in 41 patients at diagnosis (80 percent), 31 (61 percent) had lost a sex chromosome, seven (14 percent) showed a partial deletion of the long arm of chromosome 9 and in three patients (6 percent) a gain of chromosome 8 was observed. Whereas the loss of a sex chromosome had no influence on prognosis, a partial deletion of the long arm of chromosome 9 was an unfavorable prognostic factor. The median overall survival of the seven patients with del(9q) was only 12.5 months and thus significantly shorter than in patients with only t(8;21) or with t(8;21) and additional sex chromosome loss (median survival not reached: P = 0.0010).

Acute Disease↗

PubMed1996

Refined chromosomal localization of the human thrombopoietin gene to 3q27-q28 and exclusion as the responsible gene for thrombocytosis in patients with rearrangements of 3q21 and 3q26.

Thrombocytosis is a characteristic clinical feature in patients with myelocytic malignancies and chromosomal rearrangements of 3q21 and 3q26, sometimes called the '3q21q26 syndrome'. The function of thrombopoietin (TPO) in megakaryocytopoiesis and thrombopoiesis as well as its chromosomal location, marked TPO as a candidate gene for malignancies with 3q rearrangements combined with dysmegakaryopoiesis. In this study 12 cases with inv(3)(q21q26) or t(3;3)(q21;q26) were analyzed by means of PFGE, but no rearrangements near the TPO locus were detectable. Six YACs containing the TPO locus were isolated and characterized. By dual color in situ hybridization using a YAC from 3q26 containing the EVI1 gene and a YAC from the TPO locus, the localization of the human TPO gene could be refined to 3q27-q28 about 15-20 Mbp telomeric to the 3q26 breakpoints occurring in myeloid malignancies. TPO levels were analyzed in the serum of three patients and were found to be in the normal range. These results confirm the findings of two previous studies that thrombopoietin expression is not the main cause of thrombocytosis in the 3q21q26 syndrome.

Chromosome Breakage↗

PubMed1995

Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations.

Acute myeloid leukemia (AML) is a heterogenous disease according to morphology, immunophenotype, and genetics. The retained capacity of differentiation is the basis for the phenotypic classification of the bulk population of leukemic blasts and the identification of distinct subpopulations. Within the hierarchy of hematopoietic development and differentiation it is still unknown at which stage the malignant transformation occurs. It was our aim to analyze the potential involvement of cells with the immunophenotype of pluripotent stem cells in the leukemic process by the use of cytogenetic and cell sorting techniques. Cytogenetic analyses of bone marrow aspirates were performed in 13 patients with AML (11 de novo and 2 secondary) and showed karyotype abnormalities in 10 cases [2q+, +4, 6p, t(6:9), 7, +8 in 1 patient each and inv(16) in 4 patients each]. Aliquots of the samples were fractionated by fluorescence-activated cell sorting of CD34+ cells. Two subpopulations, CD34+/CD38- (early hematopoietic stem cells) and CD34+/CD38+ (more mature progenitor cells), were screened for karyotype aberations as a marker for leukemic cells. Clonal abnormalities and evaluable metaphases were found in 8 highly purified CD34+/CD38- populations and in 9 of the CD34+/CD38- specimens, respectively. In the majority of cases (CD34+/CD38-, 6 of 8 informative samples; CD34+/CD38+, 5 of 9 informative samples), the highly purified CD34+ specimens also contained cytogenetically normal cells. Secondary, progression-associated chromosomal changes (+8, 12) were identified in the CD34+/CD38- cells of 2 patients. We conclude that clonal karyotypic abnormalities are frequently found in the stem cell-like (CD34+/CD38-) and more mature (CD34+/CD38+) populations of patients with AML, irrespective of the phenotype of the bulk population of leukemic blasts and of the primary or secondary character of the leukemia. Our data suggest that, in AML, malignant transformation as well as disease progression may occur at the level of CD34+/CD38- cells with multilineage potential.

Acute Disease↗

PubMed1995

dic(9;20): a new recurrent chromosome abnormality in adult acute lymphoblastic leukemia.

Loss of chromosome 20 and rearrangement of the short arm of chromosome 9 were identified by banding analysis of three adult patients with acute lymphoblastic leukemia (ALL). The G-banding pattern suggested an identical deletion of 9p, but, also, an unbalanced translocation with chromosome 20 was taken into consideration. Dual-color chromosome painting with probes for chromosomes 9 and 20 revealed the presence of material from chromosome 20 at the short arm of the abnormal chromosome 9 in all three cases. Centromeric alpha-satellite DNA of both chromosome 9 and chromosome 20 was demonstrated by fluorescence in situ hybridization and indicated the presence of a dicentric chromosome. The hybridization of a YAC clone of the short arm of chromosome 20 proved that the dicentric chromosome contained the short arm of chromosome 20, which had been suspected from the G-banding pattern. Thus, the rearrangement was interpreted as dic(9;20)(p11;q11.?1). Because this was the sole chromosome abnormality in two patients, dic(9;20) may be a primary chromosome aberration in ALL. In one case, a 9q+ chromosome derived from a Philadelphia (Ph) translocation was involved in the formation of the dicentric chromosome. Immunophenotyping revealed CD10+ B-cell precursor ALL in all three cases. Whereas the two patients in whom dic(9;20) was the sole cytogenetically detectable change are in continuous complete remission for 10 and 45 months, respectively, the Ph+ patient relapsed with leukemia and died 8 months after diagnosis.

Adult↗

PubMed1995

Cytogenetic findings in 179 patients with myelodysplastic syndromes.

Cytogenetic analyses were performed on 266 bone marrow and peripheral blood samples from 179 patients with myelodysplastic syndromes (MDS). According to the FAB classification, 42 patients presented with RA, 18 with RARS, 37 with RAEB, 22 with CMML, and 29 with RAEB-T. Nine patients showed a secondary MDS (S MDS). FAB classification was not available for 22 patients. Clonal karyotype anomalies were found in 92 patients (51.4%). Complex chromosome abnormalities occurred in 17 (18.5%) of them. An evolution of the karyotype was detected in 16 cases (17.4%). Cytogenetically independent cells or cell clones were found in eight patients. Nonclonal chromosome abnormalities were uncovered in 29 (16.2%) of the 179 MDS patients. Consecutive studies were performed in 48 patients and revealed a good correlation of initial karyotype and clinical course. The most frequent single anomalies were 5q- in 29 (31.5%), -7 in 22 (23.9%), trisomy 1q in 14 (15.2%), and +8 in 13 (14.1%) of 92 patients respectively. Our cytogenetic findings are presented in detail and discussed in relation to patients' age, morphological classification, clinical course, and prognostic impact. The contribution of cytogenetic findings to the delineation of multistep pathogenesis of MDS with special emphasis to karyotype instability is demonstrated.

Adult↗

PubMed1995

Twenty-three cases of acute lymphoblastic leukemia with translocation t(4;11)(q21;q23): the implication of additional chromosomal aberrations.

The translocation t(4;11)(q21;q23) is one of the most common specific chromosomal aberrations in acute lymphoblastic leukemia (ALL), occurring in 2% of childhood and in 5-6% of adult cases. Especially in adults, the t(4;11) is associated with a poor prognosis. In order to determine the significance of clonal chromosome aberrations that occur in addition to t(4;11), we studied the karyotypes and clinical courses of 23 patients with acute lymphoblastic leukemia and a translocation t(4;11)(q21;q23). Additional clonal chromosome aberrations were found in ten patients. An isochromosome i(7)(q10) and a trisomy 6 were observed most frequently as secondary anomalies. Clonal evolution was detected in four of six patients analyzed at diagnosis as well as at relapse. With treatment carried out according to modern risk-adapted therapy protocols, no difference in outcome was observed between patients with clonal chromosome aberrations in addition to t(4;11) at diagnosis and those without.

Adolescent↗

PubMed1995

Establishment and characterization of a novel CD34-positive human myeloid leukemia cell line: MHH225 growing in serum-free culture.

A new human multilineage myeloid leukemia cell line, MHH225, has been established in our laboratory from the bone marrow of a 60-year-old patient suffering from acute megakaryoblastic leukemia (M7); it provides a unique model for studying the effect of biologic and chemical agents on the lineage specificity of a multipotent myeloid leukemia clone containing a mixed population of megakaryoblast, erythroblast, and myeloblast cells in a serum-free culture. Morphologically, all 225 cells are large blast cells with basophilic cytoplasm containing no granules, large round nucleus containing 2-3 prominent nucleoli, and fine chromatin structure and a large nuclear/cytoplasm ratio. The MHH225 cells are CD34+HLA-DR+CD33+CD13+ with 57.6%, 28.3%, and 7.8% of them being CD41+, glycophorin A+, and CD15+, respectively, and all lymphoid-specific antigens are negative. The karyotype analysis of MHH225 cells revealed a deletion of the short arm of chromosome 7: del(7)(p13)-, a whole-arm translocation between the long arms of chromosomes 9 and 21: t(9;21)(q10;q10), and a chromosome 11 with an elongated long arm due to duplication of chromosome 11 material as well as to translocation of part of chromosome 9 onto 11q+. Also, chromosome 21 was deleted in some metaphases or showed a ring formation in other metaphases. Utrastructurally, MHH25 cells display a strong platelet peroxidase activity in the nuclear envelope and the endoplasmic reticulum. The MHH25 cells have been grown exponentially without growth factors or conditioned media or serum only in RPMI1640 culture medium. None of the myelopoietic growth factors, i.e., interleukin-3, GM-CSF, G-CSF, erythropoietin, or interleukin-6, has any effect on the proliferation and differentiation of MHH25 cells. The two, hematopoietic inhibitory cytokines, interferon-alpha and tumor necrosis factor-alpha, have only minimal growth inhibitory effect. Stem cell factor showed only weak growth-stimulatory effect on MHH225 cells but significantly inhibited chemotherapy-induced apoptosis in these cells. The new cell line MHH225 should constitute a useful model for studying stem cell antigen (CD34)-positive human multilineage myeloid leukemia cells carrying a deletion in the short arm of chromosome 7 and an aberration in chromosome 11 and provide a unique tool for investigating human hematopoietic stem cell biology and its cytokine regulation in serum-free cultures. To our knowledge, the MHH225 cell line is the first human CD34-positive leukemia cell line growing in serum-free cultures to be established.

Antigens, CD34↗

PubMed1995

The fusion of TEL and ABL in human acute lymphoblastic leukaemia is a rare event.

We have recently identified a common ALL patient which harboured a chromosomal fusion between the TEL gene on chromosome 12 and the ABL gene on chromosome 9. We designed an RT-PCR assay to screen 186 adult ALL and 30 childhood ALL patients for this novel translocation. We were unable to identify any additional cases with a TEL/ABL fusion product.

Adult↗

PubMed1995

Localization of the undulin gene (UND) to human chromosome band 8q23.

Undulin, a large extracellular matrix (ECM) mosaic glycoprotein related to collagen type XIV, is associated with dense collagen matrices in soft tissues and is likely to be involved in the supramolecular organization of interstitial collagens. By fluorescence in situ hybridization (FISH), we have assigned the undulin locus (UND) to band q23 of human chromosome 8.

Chromosome Mapping↗

PubMed1995

17p anomalies in lymphoid malignancies: diagnostic and prognostic implications.

Eighteen patients with lymphoid malignancies and abnormalities of the short arm of chromosome 17 were evaluated, in order to analyse whether this anomaly was associated with a particular subgroup of lymphoid malignancies. The patients suffered from acute lymphoblastic leukemia, high-grade non-Hodgkin's lymphoma or plasma cell leukemia. No 17p anomaly was found in any patient with chronic lymphocytic leukemia or low-grade non-Hodgkin's lymphoma. In four cases the aberration of the short arm of chromosome 17 was the sole cytogenetic abnormality, in fourteen patients additional chromosomal aberrations were found. Five out of 18 cases were Burkitt's lymphoma/leukemia showing the typical rearrangement of 8q24. In cases with a karyotype evolution the 17p anomaly was always a late event. Concerning the clinical outcome of the patients with abnormalities of the short arm of chromosome 17 eight of nineteen patients died within 90 days after the diagnosis of the 17p anomaly only three were alive at the last follow up (26 months to 40 months after diagnosis of a 17p aberration). Rearrangements of 17p, especially as secondary cytogenetic events, seem to be associated with a poor clinical outcome in lymphoid malignancies.

Adolescent↗

PubMed1995

Clinical, morphologic, cytogenetic and prognostic implications of CD34 expression in childhood and adult de novo AML.

Expression of CD34 by leukemic blasts was analyzed in 230 pediatric and 251 adult patients with de novo AML enrolled in two large multicenter trials (AML-BFM-87 and AMLCG respectively). The association between CD34 positivity and morphological classification according to FAB criteria, cytogenetic aberrations, immunophenotypic features and clinical characteristics was investigated. CD34 was expressed (> or = 20%) by leukemic cells from 45% of childhood and 43% of adult AML patients. CD34+ AML was often associated with M1/M2 morphology as well as the coexpression of CD7 and TdT. Translocation t(8;21), inv(16) and chromosome 5 and 7 aberrations were more frequently observed in CD34+ AML. There was a low frequency of CD34 expression in infant AML but no age dependency was evident in adult patients. CD34 expression exerted no influence on the rate of complete remissions (CR) after intensive multidrug induction therapy. In adults, 56% of the CD34-positive and 64% of CD34-negative cases achieved CR (P = 0.29), and the childhood trial even revealed a slight advantage for CD34+ AML with a CR rate of 80% vs. 71% for CD34-negative cases (P = 0.068). Long-term follow-up disclosed no significant differences in remission duration or event-free survival between the CD34-positive and CD34-negative groups. In conclusion, CD34+ AML patients comprise a heterogeneous group with good as well as poor risk factors. Though characterized by some distinct features, CD34 lacks prognostic significance in de novo AML patients submitted to intensive polychemotherapy.

Adolescent↗

PubMed1995

G-CSF in the long-term treatment of cyclic neutropenia and chronic idiopathic neutropenia in adult patients.

Eleven adult patients with chronic neutropenia have been treated with recombinant human granulocyte colony-stimulating factor (G-CSF). Seven patients had idiopathic sporadic neutropenia, 2 idiopathic congenital neutropenia and 2 cyclic neutropenia. Treatment was started with 3 micrograms/kg s.c. daily and was modified according to response. All patients had a rapid increase of neutrophils. The cycle length shortened from 21 to 14 days in patients with congenital cyclic neutropenia. Doses required for maintenance ranged from 0.1 to 8 micrograms/kg. One patient with idiopathic sporadic neutropenia recovered after 151 days with an absolute neutrophil count (ANC) of > 2000/microliters and had no need for further treatment. The overall efficacy of the treatment was good with abrogation of severe infections. Treatment has been continuously given to a maximum of 4.5 years. No loss of efficacy was observed during long-term treatment. There was no evidence for lineage drain or stem cell exhaustion with prolonged treatment. Cytogenetic analyses in seven of eleven patients did not reveal the development of abnormal cell-clones. G-CSF is safe and efficient in long-term treatment of adult patients with chronic neutropenias.

Adult↗

PubMed1994

Pre-pre-B acute lymphoblastic leukemia: high frequency of alternatively spliced ALL1-AF4 transcripts and absence of minimal residual disease during complete remission.

We used the polymerase chain reaction (PCR) to detect ALL1-AF4 rearrangements, the molecular hallmark of t(4;11) in a series of 46 pre-pre-B (CD19+, CD24+, CD10/CD20/cylgM/sIgM-) acute lymphoblastic leukemias (ALL). Eighteen patients (39%) exhibited fusion transcripts including 4 of 12 children and 14 of 34 adults. This genetic defect was associated with hyperleukocytosis (median leukocyte count 176 x 10(9)/L) and expression of myeloid-associated antigens (CDw65+). In contrast, only two patients from a group of 67 common (CD19/CD10+, cylgM/sIgM-) and pre-B ALLs (CD19/cylgM+, CD10 +/-, sIgM-) showed ALL1-AF4 mRNA. All PCR-positive cases showed multiple amplification products representing alternative splicing events. Moreover, reciprocal der (4)-derived AF4-ALL1 transcripts were observed in 65% of the cases analyzed. Eight of the 18 pre-pre-B ALL patients with an ALL1-AF4 recombination are currently in complete continuous remission for up to 54 months (median, 26 months). Twelve remission samples were available from seven cases, and all of them lacked evidence of minimal residual disease. Overall this study documents a similarly high incidence of ALL1-AF4 recombinations in children (infants excluded) and adults with pre-pre-B ALL and demonstrates the decline of the leukemic cell clone below the detection level of PCR in a remarkable proportion of patients under intense treatment protocols.

Adolescent↗

PubMed1994

Characterization of five new cell lines derived from human primitive neuroectodermal tumors of the central nervous system.

Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood but only a few cell lines and animal models of this primitive neuroectodermal tumor (PNET) have thus far been established. Using specific cell culture conditions, we were able to derive four human MB cell lines (MHH-MED-1-4) as well as a cell line from a spinal PNET (MHH-PNET-5). The four MB cell lines grew in suspension as floating cell aggregates or as slightly adherent cells. They consisted of undifferentiated cells that did not express markers of late neuronal or glial lineages such as neurofilaments or glial fibrillary acidic protein. They also lacked expression of major histocompatibility complex class I or II antigens on the cell surface. All four MB lines were positive for vimentin and neuron-specific enolase, whereas synaptophysin, neural cell adhesion molecule, galactocerebroside, GD2, GD3, and the A2B5 antigen were expressed inconsistently. In contrast, MHH-PNET-5 grew as adherent monolayer and expressed major histocompatibility complex class I antigen. By cytogenetic analysis, the lines were near diploid with clonal aberrations. The MB lines showed no losses of chromosome arm 17p by either cytogenetic or microsatellite analyses. The cell line MHH-MED-2 exhibited double minute chromosomes, amplification of the c-myc gene, and overexpression of c-myc mRNA and protein. N-myc, p53, and Rb protein expression were unaltered. All four continuously passaged MB cell lines and the MHH-PNET-5 line were xenotransplanted s.c. into athymic mice; three of four MB lines and the spinal PNET line gave rise to tumors. These cell lines will be useful tools for biological and preclinical studies on PNETs.

Animals↗

PubMed1994

The human OX40 homolog: cDNA structure, expression and chromosomal assignment of the ACT35 antigen.

Tissue distribution and expression on mitogen and virally stimulated lymphocytes render the ACT35 molecule a human lymphocyte activation antigen which as yet could not be clustered. Expression cloning of the ACT35 antigen from a pCDM8 library of the HUT-102 cell line revealed strong homology of the cDNA and its encoded protein sequence with the formerly described rat OX40 antigen. The 1.4-kb nucleotide sequence and the deduced 277-amino acid sequence of the single transmembrane protein were 65% and 63% identical, in human and in rat, respectively. Conservation included one N-linked glycosylation site and one protein kinase C phosphorylation site. When expressed in COS-1 cells, the cDNA presented properties comparable to the native ACT35 antigen and the rat OX40 molecule (relative molecular mass 48,000). Thus, the ACT35 protein corresponds to the hitherto unknown human OX40 antigen and is, therefore, another member of the tumor necrosis factor/nerve growth factor receptor (TNFR/NGFR) family. After applying fluorescence in situ hybridization, the human ACT35/OX40 gene could be mapped to chromosome band 1p36 and is, thus, linked to the genes for TNFR II and CD30.

Amino Acid Sequence↗

PubMed1994

The human vigilin gene: identification, chromosomal localization and expression pattern.

Chick vigilin cRNA clones were used to isolate the cognate human gene, by screening a pWE15 genomic library. Three independent cosmid clones were isolated and characterized by restriction mapping. The gene was identified by sequencing an internal EcoRI fragment containing two exons homologous to exon 24 and 25 of the chicken vigilin gene and corresponding to nucleotides 1973-2104 of the human HBP-cDNA. The homology between the chicken and human sequences was 77% and 82% at the cDNA level, and 91% and 100% at the amino acid level. In addition, the analyzed intron/exon boundaries were invariantly conserved. The 5' and 3' regions of the human gene were mapped by Southern analysis of the respective clones with synthetic oligonucleotides. The entire vigilin gene spans a region of about 50 kb and has been assigned to chromosome 2q36-q37.2 (FL-pter value of 0.96 +/- 0.03) by fluorescence in situ hybridization to metaphase spreads from normal peripheral blood lymphocytes. The vigilin gene is localized in a chromosomal region comprising a cluster of collagen genes (COLIVA3, COLVIA3) and the locus of the Waardenburg syndrome I. Only one mRNA species of 4.4 kb is transcribed from the human vigilin gene. In accordance with previous observations on chicken mRNA, the expression of the human vigilin mRNA depends on the stage of cytodifferentiation both in vitro and in situ.

Blotting, Northern↗