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G Transition (g + transition)
Selected AbstractsAbsence of p16 and p27 gene rearrangements and mutations in de novo myelodysplastic syndromesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2005Sotirios G. Papageorgiou Abstract:, Myelodysplastic syndromes (MDS) represent a group of clonal hematopoietic disorders characterized by dyshemopoiesis and frequent evolution to acute leukemia. Tumor suppressor gene inactivation may be involved in MDS pathogenesis. The two families of cyclin-dependent kinase inhibitors (CDKIs) (INK4 family of p15, p16, p18 and p19 and CIP/KIP family of p21, p27 and p57) that negatively regulate cell cycle progression are known tumor suppressor genes. To determine whether genetic alterations of p16 and p27 genes play an important role in MDS pathogenesis, we examined DNA from 51 patients classified as 17 refractory anemias (RA), four refractory anemias with ringed sideroblasts (RARS), 19 refractory anemias with an excess of blasts (RAEB), 5 refractory anemias with excess of blasts in transformation (RAEB-t) and 6 chronic myelomonocytic leukemias (CMML). Southern blot analysis detected no homozygous deletions of p16 and p27. Polymerase chain reaction,single-strand conformation polymorphism (PCR,SSCP) and sequencing did not reveal point mutations for both genes with the exception of two allelic polymorphisms, namely a C , G transition at 447 bp of p16exon3 and a T , A transition at 791 bp of p27exon1 genes. Our results suggest that mutations of p16 and p27 genes resulting in abnormal p16 and p27 proteins do not represent a mechanism of gene inactivation involved in the pathogenesis of MDS. [source] Identification of novel single nucleotide polymorphisms within the NOTCH4 gene and determination of association with MHC allelesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2003R. Tazi-Ahnini Summary Mapping of disease susceptibility loci within the MHC has been partly hampered by the high degree of polymorphism of the HLA genes and the high level of linkage disequilibrium (LD) between markers within the MHC region. It is therefore important to identify new markers and determine the level of LD between HLA alleles and non-HLA genes. The NOTCH4 gene lies at the centromeric end of the MHC class III region, approximately 335 kb telomeric of the DRB1 locus. The encoded protein is an oncogene that is important in regulating vascular development and remodelling. A recent report has linked polymorphisms within NOTCH4 with risk of developing schizophrenia. We have investigated if coding polymorphisms exist within this gene and have identified three single nucleotide polymorphisms; a synonomous T to C transition at +1297 (HGBASE accession number SNP000064386), a synonomous A to G transition at +3061 (SNP000064387) and an A to G transition at +3063 which results in a replacement of glycine with aspartic acid at amino acid 279 (SNP000064388). The allele frequencies of +1297T, +3061A and +3063G were 0.65, 0.66 and 0.66, respectively. Linkage disequilibrium was detected both between these markers and with MHC alleles. These findings can be used in the fine mapping of disease susceptibility alleles within the MHC. [source] A New De Novo Missense Mutation in Connexin 26 in a Sporadic Case of Nonsyndromic DeafnessTHE LARYNGOSCOPE, Issue 5 2007Paola Primignani PhD Abstract Objectives: Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic recessive deafness or dominant hearing loss (HL) with or without keratoderma. The objective was to perform a molecular evaluation to establish the inherited pattern of deafness in the sporadic cases afferent to our center. Methods: The subject was a 2-year-old Italian girl with nonsyndromic early onset HL. We performed DNA sequencing of the GJB2 gene and deletion analysis of the GJB6 gene in all family members. Results: Direct sequencing of the gene showed a heterozygous C,G transition at nucleotide 172 resulting in a proline to alanine amino acid substitution at codon 58 (P58A). The analyses indicate that the P58A mutation appeared de novo in the proband with a possible dominant effect. Conclusions: This mutation occurs in the first extracellular domain (EC1), which seems to be very important for connexon-connexon interaction and for the control of voltage gating of the channel. The de novo occurrence of an EC1 mutation in a sporadic case of deafness is consistent with the assumption that P58A can cause dominant HL. [source] Is the mitochondrial complex I ND5 gene a hot-spot for MELAS causing mutations?ANNALS OF NEUROLOGY, Issue 1 2003Danae Liolitsa PhD We identified two novel heteroplasmic mitochondrial DNA point mutations in the gene encoding the ND5 subunit of complex I: a 12770A,G transition identified in a patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) and a 13045A,C transversion in a patient with a MELAS/Leber's hereditary optic neuropathy/Leigh's overlap syndrome. Biochemical analysis of muscle homogenates showed normal or very mildly reduced complex I activity. Histochemistry was normal. Our observations add to the evidence that mitochondrial ND5 protein coding gene mutations frequently associate with the MELAS phenotype, and it highlights the role of complex I dysfunction in MELAS. Ann Neurol 2003 [source] Radiation-induced cutaneous carcinoma of the head and neck: is there an early role for p53 mutations?CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2006A. Franchi Summary Background., Little is known about the molecular mechanisms underlying ionizing radiation-induced carcinogenesis of the skin. Aims., To investigate the possible role of p53 in radiodermatitis and in the development of radiation-induced cutaneous carcinomas. Methods., The study group comprised six patients affected by cutaneous carcinomas arising in radiodermatitis (one squamous cell carcinoma and five basal cell carcinomas), and seven patients presenting only chronic radiodermatitis. Skin specimens were evaluated for p53 immunohistochemical expression. Using laser-assisted microdissection, areas with different p53 immunoreactivity were separately submitted to DNA isolation and p53 gene analysis. Results., In the majority of cases (9/12, 75%), p53 immunoreactivity was detected in radiation-damaged epidermis. In carcinomas p53 oncoprotein was expressed by several neoplastic cells in one case (16.7%%), or by nearly all neoplastic cells in four (66.7%). SSCP band shifts were detected in 9/25 samples (36%) microdissected from irradiated epidermis and in 3/6 (50%) carcinomas. DNA sequencing demonstrated two repeatedly found mutations: a G deletion at codon 244 and an A,G transition at codon 205, as well as hallmarks of ultraviolet mutagenic action, including a C,T transition occurring at a dipyrimidine site and a CC,TT tandem double-base transition. Conclusion., Our data indicate that irradiation induces significant p53 alterations that may be relevant in the modification of epithelial maturation processes and may be responsible for the high risk for development of carcinomas in radiodermatitis. [source] A to G transitions at 260, 386 and 437 in DAZL gene are not associated with spermatogenic failure in Indian populationINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2006K. Thangaraj Summary The autosomal DAZL (Deleted-in- Azoospermic- Like) gene, mapped to the short arm of the human chromosome 3, is the precursor for the Y-chromosomal DAZ cluster, which encodes for putative RNA-binding proteins. Mutations in the DAZL have been reported to be associated with spermatogenic failure in Taiwanese population but not in Caucasians. As there was no study on Indian populations, we have analysed the entire coding sequences of exons 2 and 3 of DAZL in a total of 1010 men from Indian subcontinent, including 660 infertile men with 598 non-obstructive azoospermia, 62 severe oligozoospermia and 350 normozoospermic fertile control men, to investigate whether mutation(s) in the DAZL is associated with male infertility. Interestingly, none of our samples (1010) showed A386G (T54A) mutation, which was found to be associated with spermatogenic failure in Taiwanese population. In contrast, A260G (T12A) mutation was observed in both infertile and normozoospermic fertile control men, without any significant association with infertile groups (,2 = 0.342; p = 0.556). Similarly, we have found a novel A437G (I71V) mutation, which is also present in both infertile and normozoospermic fertile control men without any significant difference (,2 = 0.476; p = 0.490). Our study clearly demonstrates the complete absence of the A386G (T54A) mutation in Indian subcontinent and the other two mutations , A260G (T12A) and A437G (I71V) , observed are polymorpic. Therefore, we conclude that these mutations in the DAZL gene are not associated with male infertility in Indian subcontinent. [source] | ||||||||||