Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Celiac disease is a wheat gliadin-promoted disorder that displays a complex genetic susceptibility associated with HLA-DQ2, and one or more unknown factor(s), possibly gliadin-like. The presence of mammalian proteins with partial gliadin similarity was suggested by transglutaminase-independent multi-tissue reactivity of gliadin-immunopurified antibodies from celiac patients. No non-plant sequence, however, was identified in gliadin peptide epitope searches of non-redundant and EST databanks via TBLASTN, BLASTP and FASTA, even at E values as high as 20. Therefore, an alpha-gliadin cDNA screen of human cDNA and genomic libraries was undertaken, an approach in keeping with positive human Northern and Southern analyses with the same probe. Four distinct cDNA clones were obtained, the most stringent of which (3.2 and 5.1 kb) were novel, and featured potential open reading frames with high gliadin domain II and domain IV homologies (BestFit quality scores >/=295 and 322, respectively, versus random value 126-127). Both were also homologous to ESTs. An additional 5' gliadin oligonucleotide screen identified the widely distributed cytoplasmic protein acyl coA hydrolase whose homology was restricted to the oligonucleotide probe (BestFit quality=215 versus 100 for random); and achaete-scute homologous protein, which displays particularly high gliadin domain II homology (BestFit quality 316 versus 111 for random). Genomic screening uncovered 16 positives, one of which was the ALR gene, whose similarity to three of gliadin's five domains (I, II and IV; BestFit quality 322-473 versus 121-154 for random) was remarkable. More extensive was novel genomic clone 2, with fragments hybridizing to cDNA probes approximating gliadin domains I, II+IV, V and the gliadin 5' untranslated region, and mapping by FISH to 19q13.11-13. 12. Two fragments were sequenced; one was exonic, as predicted by four different programs; and test oligonucleotides suggested widespread 4 and/or 2 kb mRNA expression, even at high stringency (t(m)-8.8 deg. C). Taken together, it is apparent that several genes with partial gliadin homology exist in the human genome. Many bear gliadin-like T-cell epitopes, are expressed in intestine and, like transglutaminase, are cytoplasmic. Glutamine to glutamic acid or other mutation within such epitopes followed by injury or infection-related release could explain enhanced disease susceptibility in affected families.
J Mol Biol 2000 Jul 28
PMID:Human genome search in celiac disease using gliadin cDNA as probe. 1090 61

Charcot-Marie-Tooth disease (CMT) and hereditary neuropathy with liability to pressure palsies (HNPP) are the most frequent inherited disorders of the peripheral nervous system. They are clinically and genetically heterogeneous. A submicroscopic tandem duplication of 1. 5 Mb in chromosome 17p11.2-12 comprising the PMP22 gene is found in 70.7% of autosomal dominant Charcot-Marie-Tooth type 1 (CMT1) patients. A reciprocal deletion is found in 87.6% of HNPP patients. The size of the typical CMT1A duplication is too small for classical cytogenetics and the whole region including the CMT1A-REP elements is sometimes too complex for a single DNA analysis method. We present results of a multiplex PCR of 8 microsatellite markers with multicolour fluorescence primer labelling followed by fragment analysis on an ABI 310 Prism analyzer to simplify the diagnostic procedure. Results for 24 patients can be obtained within 24 h. This method was applied on 92 DNA samples of unrelated patients carrying a typical CMT1A duplication previously confirmed by two colour fluorescence in situ hybridization (FISH, probe c132G8) and EcoRI/SacI Southern blotting (probe pLR7.8). Three alleles of three different sizes were clearly detected at least once in 88 of them (95.6%). Subsequently this analysis was applied on 312 Czech patients and revealed a CMT1A/HNPP rearrangement in 109 out of them.
Int J Mol Med 2000 Oct
PMID:Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP): reliable detection of the CMT1A duplication and HNPP deletion using 8 microsatellite markers in 2 multiplex PCRs. 1099 31

Human Fas associated factor 1 protein (hFAF1) is involved in the positive regulation of Fas signaling even though it can not initiate the signal for itself. By chromosomal assignment using somatic cell hybrids (CASH), the hFAF1 gene was located on human chromosome 1 between markers D1S443 and D1S197. The hFAF1 gene was mapped to human chromosome band 1p32 by FISH utilizing a genomic PAC clone containing the gene. In genomic Southern analysis using hFAF1 cDNA as a probe, several bands appeared in three different restriction enzyme digestions. The single band appearance in FISH analysis compared to several bands in Southern blots implies that the hFAF1 gene would be rather big or that an additional hFAF1 gene isotype(s) might be present in close vicinity.
Mol Cells 2000 Oct 31
PMID:Human Fas associated factor 1, hFAF1, gene maps to chromosome band 1p32. 1110 Nov 54

The possibility to employ cryopreservation in Preimplantation Genetic Diagnosis (PGD) should enlarge the opportunities for research and clinical activity. For these purposes, we tried three kinds of approaches on human abnormal embryos: (1) cryopreservation of biopsied embryos; (2) biopsy of thawed embryos; and (3) biopsy of embryos derived from thawed oocytes. Our preliminary results show that: (1) biopsy of thawed embryos is feasible and FISH analysis is possible on both survived and lysed cells; (2) Optimization of freezing/thawing procedures are necessary to obtain better survival rate after thawing of biopsied embryos; (3) Biopsy and FISH are feasible on embryos derived from thawed oocytes and they could be a good way to study the chromosomal arrangement of these poorly investigated embryos.
Mol Cell Endocrinol 2000 Nov 27
PMID:Micromanipulation of cryopreserved embryos and cryopreservation of micromanipulated embryos in PGD. 1115 56

Histopathological differentiation between hepatocellular adenoma and well differentiated hepatocellular carcinoma (HCC) may be a difficult task in small biopsies and occasionally in resected tumor specimens. Whether the analysis of chromosome aberrations can contribute to a more precise discrimination has not been analyzed systematically up to now. Therefore, fluorescence in situ hybridization was applied to 28 cases of adenoma and well differentiated carcinoma, using centromeric probes for chromosomes 1, 6, 7, 8, and X. None of 14 adenomas revealed an aberrant count in the analyses performed. By contrast, 13/14 carcinomas demonstrated aberrations for 2-5 chromosomes/case. Chromosome 1 was aberrant in 8/12 cases informative for this probe (67%), chromosomes 6 and 7 were aberrant in 9/14 cases (64%), chromosome 8 was aberrant in 11/14 cases (79%), and chromosome X in 7/14 cases (50%). Taking results for chromosomes 1 and 8 together, 13/14 HCC revealed aberrations for at least one of these chromosomes. Probes for 6, 7, and X revealed no additional aberrant cases.Thus, FISH for chromosomes 1 and 8, extended by probes for chromosomes 6, 7 and X, represents a promising approach toward a more accurate differentiation between hepatocellular adenoma and carcinoma.
J Mol Diagn 2001 May
PMID:Diagnostic impact of fluorescence in situ hybridization in the differentiation of hepatocellular adenoma and well-differentiated hepatocellular carcinoma. 1133 2

The tumor suppressor genes p15INK4B and p16INK4A, located in the chromosomal region 9p21, are frequently inactivated by homo- or hemizygous deletions, point mutation or promotor methylation in various types of cancer. No commercial probe is yet available that allows the detection of such deletions by FISH. Long distance (LD)-PCR was successfully used to generate a FISH probe, that covers a sequence stretch of 11.68 kb, located between the tumor suppressor genes p15 and p16. The LD-PCR amplicon was cloned and biotinylated by DOP-PCR (degenerated oligonucleotide primed-PCR) or nick translation. The FISH probe was hybridized on different samples of 16 patients with leukemia (3 T-ALL, 13 CML) and normal controls. Loss of at least one FISH-signal was found in 2/3 (67%) of the T-ALL- and 2/13 (15%) of the CML-cases. The new FISH probe presented here was proven to be advantageous for the detection of deletions in chromosomal region 9p21, especially between p15 and p16.
Int J Mol Med 2001 Jun
PMID:A long distance-PCR derived FISH probe detects a deletion between p15 and p16 in CML and T-ALL patients. 1135 Dec 70

Velo-cardio-facial syndrome (VCFS) has been associated with schizophrenic symptoms in some patients and is caused by a deletion of 22q11.21--q11.23. The voltage-gated calcium channel (VGCC) gamma 2 subunit is located on chromosome 22 and is telemeric to the most commonly observed VCFS deletion region but is near a putative marker for schizophrenia (D22S278). Metaphase spreads of four controls, four patients with VCFS, and one patient with VCFS and schizophrenia were evaluated for the VCFS deletion using the VCFS-diagnostic probe, TUPLE 1, and for deletion of VGCC gamma 2 subunit gene using probes for that gene's exon 1 and exons 3 and 4. All of the VCFS patients had deletion of the TUPLE 1 probe on one chromosome of the chromosome 22 pair. None showed deletion of the gamma 2 subunit exons studied. The location of the gamma 2 subunit gene at 22q13.1 was confirmed by FISH in all cases. This study did not show a deletion of the gamma 2 subunit gene as a distinguishing feature of our patient with VCFS and schizophrenia.
Mol Psychiatry 2001 Jul
PMID:Voltage-gated calcium channel gamma 2 subunit gene is not deleted in velo-cardio-facial syndrome. 1144 34

This report describes an intriguing combination of the thyroid peroxidase (TPO) alleles resulting in an iodide organification defect. Sequence analysis of the patient's TPO gene showed the presence of T-deletion in exon 14 of the TPO gene (T2512del). From the sequencing pattern, this new mutation of the TPO gene was thought to be homozygous. mRNA transfection studies in which mutated mRNA was transfected to CHO-K(1) cells by electroporation showed that the cells transfected with mutated mRNA expressed smaller TPO molecules than those of cells transfected with wild-type mRNA and that they had TPO activity. However, the smaller TPO molecules could not translocate onto the cell surface. To investigate T2512del in the parents, their genomic DNAs were sequenced. Results showed that the mother had T2512del but the father did not. However, when seven polymorphic positions reported earlier were analyzed, the mother showed two kinds of nucleotides at four positions but the patient and father showed only one nucleotide at all seven positions. We suspected a deletion of the TPO gene (2p25) in one of two second chromosomes, and analyzed the patient's chromosomes by FISH using TPO cDNA and N-myc genomic DNA as probes. N-myc genomic DNA exhibited two signals and TPO cDNA only one signal, although the G-band showed no morphological abnormalities. T2512-deleted and 2p25-deleted null alleles cosegregated from her parents, resulting in iodide organification defect in the patient.
Mol Cell Endocrinol 2001 Aug 20
PMID:Iodide organification defects resulting from cosegregation of mutated and null thyroid peroxidase alleles. 1150 Feb 39

Bacillus stick insects have proved adequate for studying a wide array of reproductive modes: sexual, parthenogenetic, hybridogenetic, androgenetic. Hybridogenetic strains (B. rossius-grandii) were thought to discard the paternal "grandii" haploset during first meiotic division and keep the "rossius" hemiclone, whereas the clonal B. whitei (=rossius/grandii) would maintain its hybrid structure by fusing back two nonsister nuclei-each derived from previously segregated heterospecific complements-by the end of the 2(nd) meiotic division. New investigations on laid eggs and ovariole squashes, either DAPI stained or FISH labeled, revealed that in hybridogens the "grandii" set is excluded from the germ line prior to meiosis and that a DNA extra-synthesis should occur to produce hemiclonal eggs after two cytologically normal meiotic divisions. On the other hand, in B. whitei eggs no genome segregation appears to occur and an intrameiotic DNA extra-synthesis must take place to produce 2n tetrachromatidic oocytes I; these divide twice and give unreduced clonal eggs. The new findings bring hybridogenetic oogenesis of Bacillus to be coincident with that of the known hemiclonal organisms and point to an independent onset of B. whitei from hemiclonal strains. In addition, B. whitei gains a closer resemblance to B. lynceorum owing to the sharing of a cytologically identical egg maturation mechanism, of the same maternal ancestor and of peculiar chromosomal features. It is here suggested that B. lynceorum originated from the incorporation of an "atticus" genome into a B. whitei egg, according to a pathway of repeated hybridization often occurred with other polyploid hybrids.
Mol Reprod Dev 2001 Oct
PMID:New DAPI and FISH findings on egg maturation processes in related hybridogenetic and parthenogenetic Bacillus hybrids (Insecta, Phasmatodea). 1155 28

Single cell genetic analysis is generally performed using PCR and FISH. Until recently, FISH has been the method of choice. FISH however is expensive, has significant misdiagnosis rates, can result in interpretation difficulties and is labour intensive making it unsuitable for high throughput processing. Recently fluorescent PCR reliability has increased to levels at or surpassing FISH whilst maintaining low cost. However, PCR accuracy has been a concern due to allelic dropout. Multiplex PCR can now increase accuracy by using multiple markers for each chromosome to firstly provide diagnosis if markers fail and/or secondly confirm diagnosis. We compare a variety of diagnostic methods and demonstrate for the first time a multiplex PCR system providing simultaneous diagnosis and confirmation of the major aneuploidy chromosomes (21,18,13) and sex as well as DNA fingerprint in single cells. We also discuss the implications of using PCR for aneuploidy screening in preimplantation genetic diagnosis.
Mol Cell Endocrinol 2001 Oct 22
PMID:Using MF-PCR to diagnose multiple defects from single cells: implications for PGD. 1157 25


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