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C C Morton

Publications and source records attributed to C C Morton.

At least 91 records · Page 5Linked to original sources
PubMed1997

Genomic organization, complete sequence, and chromosomal location of the gene for human eotaxin (SCYA11), an eosinophil-specific CC chemokine.

Eotaxin is a CC chemokine that is a specific chemoattractant for eosinophils and is implicated in the pathogenesis of eosinophilic inflammatory diseases, such as asthma. We describe the genomic organization, complete sequence, including 1354 bp 5' of the RNA initiation site, and chromosomal localization of the human eotaxin gene. Fluorescence in situ hybridization analysis localized eotaxin to human chromosome 17, in the region q21.1-q21.2, and the human gene name SCYA11 was assigned. We also present the 5' flanking sequence of the mouse eotaxin gene and have identified several regulatory elements that are conserved between the murine and the human promoters. In particular, the presence of elements such as NF-kappa B, interferon-gamma response element, and glucocorticoid response element may explain the observed regulation of the eotaxin gene by cytokines and glucocorticoids.

Amino Acid Sequence↗
PubMed1997

Rare trisomy mosaicism diagnosed in amniocytes, involving an autosome other than chromosomes 13, 18, 20, and 21: karyotype/phenotype correlations.

In order to determine the significance of trisomy mosaicism of an autosome other than chromosomes 13, 18, 20, and 21, 151 such cases diagnosed prenatally through amniocentesis were reviewed. These rare trisomy mosaicism cases include 54 from 17 cytogenetic laboratories, 34 from a previous North American mosaicism survey, and 63 from published reports. All were cases of true mosaicism with information available on pregnancy outcome, and with no evidence of biased ascertainment. There were 11 cases of 46/47, +2; 2 of 46/47, +3; 2 of 46/47, +4; 5 of 46/47, +5; 3 of 46/47, +6; 8 of 46/47, +7; 14 of 46/47, +8; 25 of 46/47, +9; 2 of 46/47, +11; 23 of 46/47, +12; 5 of 46/47, +14; 11 of 46/47, +15; 21 of 46/47, +16; 7 of 46/47, +17; 1 of 46/47, +19; and 11 of 46/47, +22. As to the risk of an abnormal outcome, the data showed a very high risk (> 60 per cent) for 46/47, +2, 46/47, +16, and 46/47, +22; a high risk (40-59 per cent) for 46/47, +5, 46/47, +9, 46/47, +14, and 46/47, +15; a moderately high risk (20-39 per cent) for 46/47, +12; a moderate risk (up to 19 per cent) for 46/47, +7 and 46/47, +7 and 46/47, +8; a low risk for 46/47, +17; and an undetermined risk, due to lack of cases, for the remaining autosomal trisomy mosaics. Most cases were evaluated at birth or at termination, so subtle abnormalities may have escaped detection and developmental retardation was not evaluated at all. Comparison of the phenotypes of prenatally diagnosed abnormal cases and postnatally diagnosed cases with the same diagnosis showed considerable concordance. Since the majority of anomalies noted are prenatally detectable with ultrasound, an ultrasound examination should be performed in all prenatally diagnosed cases. In cytogenetic confirmation studies, the data showed much higher confirmation rates in cases with abnormal outcomes than in cases with normal outcomes [81 per cent vs. 55 per cent for fibroblasts (from skin, fetal tissue, and/or cord); 88 per cent vs. 46 per cent for placental cells; 22 per cent vs. 10 per cent for blood cells]. The confirmation rate reached 85 per cent when both fibroblasts and placental tissues were studied in the same case (with trisomic cells found in one or the other, or both). Therefore, one must emphasize that both fibroblasts and placental tissues should be studied. Except for 46/47, +8 and 46/47, +9, PUBS is of limited value for prenatal diagnosis of rate trisomy mosaicism. DNA studies for UPD are suggested for certain chromosomes with established imprinting effects, such as chromosomes 7, 11, 14, and 15, and perhaps for chromosomes 2 and 16, where imprinting effects are likely.

Adolescent↗
PubMed1997

Norrie disease gene mutation in a large Costa Rican kindred with a novel phenotype including venous insufficiency.

A large Costa Rican kindred has been identified with 15 males affected with congenital blindness, progressive bearing loss, and venous insufficiency. Due to ophthalmological and audio-otological findings, including bilateral retinal dysplasia and detachment, progressive bilateral sensorineural hearing loss, and an X-linked pattern of inheritance, a tentative diagnosis of Norrie disease was considered. However, venous insufficiency is a clinical finding not reportedly associated with Norrie disease. Genetic linkage analysis using microsatellite repeat markers demonstrated linkage to Xp11.23-11.4 (z = 2.723 at theta = 0.0). A candidate gene approach using the Norrie disease gene (NDP), which maps to Xp11.3, revealed a point mutation in the third exon resulting in substitution of phenylalanine for leucine at position 61. The precise function of the gene product, norrin, has yet to be elucidated; however, it has been postulated to be involved in the regulation of neural cell differentiation and proliferation, although hypotheses have been considered for its role in vascular development in the eye. The finding of a mutation in NDP in association with peripheral vascular disease may provide valuable insight into the potential role of this gene in cellular processes.

Blindness↗
PubMed1997

Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice.

Deafness is the most common form of sensory impairment in humans. Mutations in unconventional myosins have been found to cause deafness in humans and mice. The mouse recessive deafness mutation, Snell's waltzer, contains an intragenic deletion in an unconventional myosin, myosin VI (locus designation, Myo6). The requirement for Myo6 for proper hearing in mice makes this gene an excellent candidate for a human deafness disorder. Here we report the cloning and characterization of the human unconventional myosin VI (locus designation, MYO6) cDNA. The MYO6 gene maps to human chromosome 6q13. The isolation of the human gene makes it now possible to determine if mutations in MYO6 contribute to the pathogenesis of deafness in the human population.

Amino Acid Sequence↗
PubMed1997

Construction of P1-derived artificial chromosome and yeast artificial chromosome contigs encompassing the DFNB7 and DFNB11 region of chromosome 9q13-21.

DFNB7 and DFNB11, two loci for autosomal recessive nonsyndromic hearing loss (ARNSHL), have been mapped to chromosome 9q13-21 in separate consanguineous families. Using a radiation hybrid map, we have determined the correct marker order in the DFNB7/11 region and have demonstrated that the DFNB11 locus resides within a redefined DFNB7 interval. The gene(s) responsible for ARNSHL at these loci resides within an approximately 1 cM interval bounded by markers D9S1806 (centromeric) and D9S769 (telomeric). A recently discovered Indian family confirms the new telomeric boundary. To assist in the identification and cloning of candidate genes, YAC and PAC contigs were constructed. A total of 19 YAC and 23 PAC clones were utilized to span the affected region and ensure double coverage throughout. Twenty-two previously published STSs and 21 new STSs were used to determine marker order and confirm the integrity of the contig. Using a positional cloning strategy we have identified three cochlear expressed genes that map to the DFNB7/11 interval.

Chromosome Mapping↗
PubMed1997

HMGI(Y) expression in human uterine leiomyomata. Involvement of another high-mobility group architectural factor in a benign neoplasm.

Chromosomal rearrangements involving 6p21 have been observed in uterine leiomyomata and a variety of other benign tumors. The gene for HMGI(Y), a member of the high-mobility group (HMG) family of proteins, has been localized to 6p21. To determine whether rearrangements observed in this area alter HMGI(Y) expression, we analyzed HMGI(Y) DNA-binding activity in protein extracts from uterine leiomyoma and normal myometrium tissues. This report describes a uterine leiomyoma specimen with an inv(6)(p21q15). A genomic P1 clone that contains the HMGI(Y) region of chromosome 6 is found to span the inversion breakpoint by fluorescent in situ hybridization of metaphase chromosomes. Expression of HMGI(Y) protein in this leiomyoma specimen is increased dramatically as compared with the matching normal myometrial tissue. Elevated HMGI(Y) expression was also found in 8 of 16 leiomyomas without cytogenetically detectable chromosome 6p21 aberrations but not in any of the 9 matching myometrial tissues. Analysis of the genetic events involved in the pathobiology of these benign tumors will provide a basis for understanding the process of improper cellular growth and might be important in deciphering the multistep pathway of tumorigenesis.

Base Sequence↗
PubMed1997

Disseminated peritoneal leiomyomatosis. Clonality analysis by X chromosome inactivation and cytogenetics of a clinically benign smooth muscle proliferation.

Disseminated peritoneal leiomyomatosis (DPL, leiomyomatosis peritonealis disseminata) is a rare condition in which multiple histologically benign smooth muscle tumorlets diffusely stud peritoneal and omental surfaces in females, predominantly of reproductive age. Although the distribution of these lesions suggests a metastatic process, DPL generally has a benign clinical course and has been regarded as a metaplastic process. We assessed clonality of 42 tumorlets and 15 normal tissues from four females with DPL by analyzing X chromosome inactivation as indicated by the methylation status of the androgen receptor gene (HUMARA). In each of the four patients, the same parental X chromosome was nonrandomly inactivated in all tumorlets, consistent with a metastatic unicentric neoplasm, or alternatively, selection for an X-linked allele in clonal multicentric lesions. Anomalous demethylation of the marker for X inactivation (HUMARA) was associated with loss of heterozygosity for markers spanning the X chromosome, or monosomy X, in part of one leiomyomatous lesion. Biallelic demethylation of the HUMARA microsatellite polymorphism was also found in one intramural leiomyoma. Two of six DPL lesions karyotyped had cytogenetic abnormalities involving chromosomes 7, 12, and 18, suggesting a pathogenesis in common with uterine leiomyomas.

Adult↗
PubMed1996

A gene similar to PKD1 maps to chromosome 4q22: a candidate gene for PKD2.

We report a partial cDNA sequence that encodes a protein, dubbed "polycystwin," with 21% identify and 46% similarity to amino acids 3688-4109 of the carboxyl terminus of polycystin, the gene product of the autosomal dominant polycystic kidney disease locus located on chromosome 16 at band p13 (PKD1). Northern analysis demonstrates that the R48321 gene is expressed in all tissues examined, including both adult and fetal kidneys. Finally, in situ hybridization studies localize this novel gene to 4q22, where PKD2, the second most common locus for ADPKD, is known to map. Therefore, R48321 is an excellent candidate gene for PKD2.

Amino Acid Sequence↗
PubMed1996

Pleiotropic defects in ataxia-telangiectasia protein-deficient mice.

We have generated a mouse model for ataxia-telangiectasia by using gene targeting to generate mice that do not express the Atm protein. Atm-deficient mice are retarded in growth, do not produce mature sperm, and exhibit severe defects in T cell maturation while going on to develop thymomas. Atm-deficient fibroblasts grow poorly in culture and display a high level of double-stranded chromosome breaks. Atm-deficient thymocytes undergo spontaneous apoptosis in vitro significantly more than controls. Atm-deficient mice then exhibit many of the same symptoms found in ataxia-telangiectasia patients and in cells derived from them. Furthermore, we demonstrate that the Atm protein exists as two discrete molecular species, and that loss of one or of both of these can lead to the development of the disease.

Animals↗
PubMed1996

Cloning of human RTEF-1, a transcriptional enhancer factor-1-related gene preferentially expressed in skeletal muscle: evidence for an ancient multigene family.

Transcriptional Enhancer Factor-1 (TEF-1) is a transcription factor required for cardiac muscle gene activation. Since ablation of TEF-1 does not abolish cardiac gene expression, we sought to identify a human gene related to TEF-1 (RTEF-1) that might also participate in cardiac gene regulation. A human heart cDNA library was screened to obtain a full-length RTEF-1 cDNA. Fluorescence in situ hybridization assigned the RTEF-1 gene to chromosome 12p13.2-p13.3. In contrast, PCR screening of human/rodent cell hybrid panels identified TEF-1 on chromosome 11p15.2, between D11S1315 and D11S1334, extending a region of known synteny between human chromosomes 11 and 12 and arguing for an ancient divergence between these two closely related genes. Northern blot analysis revealed a striking similarity in the tissue distribution of RTEF-1 and TEF-1 mRNAs; skeletal muscle showed the highest abundance of both mRNAs, with lower levels detected in pancreas, placenta, and heart. Phylogenetic analysis of all known TEF-1-related proteins identified human RTEF-1 as one of four vertebrate members of this multigene family and further suggests that these genes diverged in the earliest metazoan ancestors.

Amino Acid Sequence↗
PubMed1996

Detection of cone alpha transducin mRNA in human fetal cochlea: negative mutation analysis in Usher syndrome.

Cone alpha transducin (GNAT2), known to be expressed in photoreceptors, was found to be transcribed in human fetal cochlea. Due to the unexpected finding of expression of this gene in the inner ear and the success of the candidate gene approach in identifying mutations for a variety of heritable disorders, we investigated the possible role of this gene in Usher syndrome type I and type II. Single-strand conformation polymorphism (SSCP) was used to screen the GNAT2 coding region, as well as splice donor and acceptor sites, for mutations in a total of 140 unrelated patients. Two nucleotide changes leading to two silent amino acid changes and one rare polymorphism were found. In view of these results and those of a previously published Southern blot analysis, it is unlikely that mutations in GNAT2 are a common gene abnormality in Usher syndrome type I or type II.

Base Sequence↗
PubMed1996

Identification, characterization, and chromosomal localization of the human homolog (hES) of ES/130.

The chicken extracellular matrix glycoprotein ES/ 130 is necessary for epithelial--mesenchymal transformation in the developing heart and is also expressed in noncardiac chicken tissues such as limb and notochord. We have identified hES, the human homolog of chicken ES/130. Fluorescence in situ hybridization analysis (FISH) localizes hES to human chromosome 20p11.2-p12. FISH analyses of individuals with 20p12 deletions and affected by Alagille syndrome exclude hES as a candidate gene for this disorder. Reverse transcriptase-polymerase chain reaction studies reveal that hES is expressed in both fetal and adult human tissues and that hES expression in the left ventricle is increased in the failing adult heart. Further studies will evaluate how hES mutations may relate to congenital human cardiac and skeletal anomalies as well as cardiac remodeling in the adult.

Adult↗
PubMed1996

The protein tyrosine phosphatase epsilon gene maps to mouse chromosome 7 and human chromosome 10q26.

We have mapped the mouse protein tyrosine phosphatase epsilon (PTP epsilon, gene symbol Ptpre) gene to the distal region of chromosome 7 by linkage analysis using two sets of multilocus genetic crosses. The human PTP epsilon gene (gene symbol PTPRE) was mapped to chromosome 10q26 by fluorescence in situ hybridization. We have previously documented the existence of two isoforms of PTP epsilon--a transmembranal, receptor-type isoform and a shorter, cytoplasmic one. Both isoforms have been suggested to arise from a single gene through the use of alternative promoters and 5' exons. The identification of a single PTP epsilon locus in both organisms is consistent with this suggestion.

Animals↗
PubMed1996

Translocation breakpoints upstream of the HMGIC gene in uterine leiomyomata suggest dysregulation of this gene by a mechanism different from that in lipomas.

Uterine leiomyomata are the most common pelvic tumors in women and are the indication for more than 200,000 hysterectomies annually in the United States. Rearrangement of chromosome 12 in bands q14-q15 is characteristic of uterine leiomyomata and other benign mesenchymal tumors, and we identified a yeast artificial chromosome (YAC) spanning chromosome 12 translocation breakpoints in a uterine leiomyoma, a pulmonary chondroid hamartoma, and a lipoma. Recently, we demonstrated that HMGIC, which is an architectural factor mapping within the YAC, is disrupted in lipomas, resulting in novel fusion transcripts. Here, we report on the localization of translocation breakpoints in seven uterine leiomyomata from 10 to > 100 kb upstream of HMGIC by use of fluorescence in situ hybridization. Our findings suggest a different pathobiologic mechanism in uterine leiomyomata from that in lipomas. HMGIC is the first gene identified in chromosomal rearrangements in uterine leiomyomata and has important implications for an understanding of benign mesenchymal proliferation and differentiation.

Chromosomes, Human, Pair 12↗
PubMed1995

Disruption of the architectural factor HMGI-C: DNA-binding AT hook motifs fused in lipomas to distinct transcriptional regulatory domains.

Lipomas are one of the most common mesenchymal neoplasms in humans. They are characterized by consistent cytogenetic aberrations involving chromosome 12 in bands q14-15. Interestingly, this region is also the site of rearrangement for other mesenchymally derived tumors. This study demonstrates that HMGI-C, an architectural factor that functions in transcriptional regulation, has been disrupted by rearrangement at the 12q14-15 chromosomal breakpoint in lipomas. Chimeric transcripts were isolated from two lipomas in which HMGI-C DNA-binding domains (AT hook motifs) are fused to either a LIM or an acidic transactivation domain. These results, identifying a gene rearranged in a benign neoplastic process that does not proceed to a malignancy, suggest a role for HMGI-C in adipogenesis and mesenchyme differentiation.

Amino Acid Sequence↗
PubMed1995

Genomic organization and chromosomal localization of the DUSP2 gene, encoding a MAP kinase phosphatase, to human 2p11.2-q11.

The mitogen-induced gene, DUSP2, encodes a nuclear protein, PAC1, that acts as a dual-specific protein phosphatase with stringent substrate specificity for MAP kinase. MAP kinase phosphorylation and consequent enzymatic activation is a central and often obligatory component in signal transduction initiated by growth factor stimulation or resulting from various types of oncogenic transformation. DUSP2 downregulates intracellular signal transduction through the dephosphorylation/inactivation of MAP kinases. To facilitate assessment of the possible role of DUSP2 in growth processes, the genomic structure and chromosomal location of the gene have been determined. DUSP2 has been localized to the pericentromeric region of human chromosome 2 (2p11.2-q11) by analysis of somatic cell hybrids, in situ chromosome hybridization, and genetic linkage analysis using a single-strand conformational polymorphism (SSCP) that has been identified in the 3' UTR of the gene. No consistent translocations or deletions at this chromosomal site have been reported in hematopoietic neoplasias or other tumors.

Base Sequence↗