Molecular characteristics and gene segment usage in IGH gene rearrangements in multiple myeloma.
David GonzálezMarcos GonzálezAna BalanzateguiMaría Eugenia SarasqueteRicardo López‐PérezCarmen ChillónRamón García‐SánzJesús F. San Miguel
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Abstract:
Analysis of IgH rearrangements in B-cell malignancies has provided clinical researchers with a wide range of information during the last few years. However, only a few studies have contributed to the characterization of these features in multiple myeloma (MM), and they have been focused on the analysis of the expressed IgH allele only. Comparison between the expressed and the non-functional IgH alleles allows further characterizion of the selection processes to which pre-myeloma cells are submitted.We analyzed a cohort of 84 untreated MM patients in order to characterize their functional VDJH and non-functional DJH rearrangements. The pattern of mutations and gene segment usage for both types of rearrangements was analyzed by polymerase chain reaction and sequencing.VH3 and VH1 family members were over- and under-represented, respectively. VH3-30 and VH3-15 segments were the most frequently used, whereas VH4-34 was found only in non-functional or heavily mutated VDJH rearrangements. DH2 and DH3 family members were over-represented in both VDJH and DJH repertoires, while the DH1 family was under-represented only in the productive VDJH rearrangements. Finally, DH3-22 and DH2-21 gene segments were found to be over-represented in the functional repertoire while segments commonly used by less mature B-cell malignancies, such as DH6-19 or DH3-3, were under-represented.Data reported here help to identify the clonogenic MM cell as a post-germinal center B cell that has undergone selection processes during the germinal center reaction.Keywords:
Gene rearrangement
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Dosage compensation
Pair-rule gene
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Afipia birgiae is an alphaproteobacterium from the family Bradyrhizobiaceae, growing in amoebae, and a potential human pathogen. We sequenced the genome of type strain 34632(T). It is composed of 5,325,467 bp and contains 5,160 protein-coding genes and 53 RNA genes, including 3 rRNA genes.
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Abstract The genetic interactions among mutations that define eight distinct loci involved in light-regulated development in Arabidopsis thaliana are described. The mutations in these eight genes define two distinct phenotypic classes with opposite characteristics. Recessive mutations in either one of two genes, DET1 or DET2, result in dark-grown plants that develop as light-grown wild-type seedlings. Mutants in the second class exhibit a reduced response to light Recessive mutations in any one of five genes, HY1, HY2, HY3, HY5, or HY6 cause reduced responses to red-light Four of these genes, HY1,2,3, and 6, affect the activity of one or all of the red-light photoreceptors, the phytochromes. The HY4 gene product is involved in blue-light perception or action. The experiments described here examine how these eight genes interact to control a particular event, the switch from developmental arrest in the dark (etiolation) to growth in the light (deetiolation). The phenotypes of doubly mutant strains suggest a hierarchical regulatory network among these genes in the control of the switch from etiolated to de-etiolated growth strategies.
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Phytoplasma
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Summary The CONSTANS ( CO ) gene of Arabidopsis plays a key role in the photoperiodic flowering pathway. To investigate photoperiod responses in cereals in more detail, we isolated three kinds of CO/Hd1 (rice ortholog of CO ) homolog from hexaploid wheat, derived from the A, B, and D genomes and designated as wheat ortholog of CO from A genome ( TaHd1‐1), TaHd1‐2 , and TaHd1‐3 , respectively. They were highly similar to each other and to Hd1 , and in addition harbored two conserved regions: two zinc finger motifs and CONSTANS, CONSTANS‐LIKE and TIMING OF CAB EXPRESSION 1 (CCT) domain like CO/Hd1 . They were located on the long arm of the homoeologous chromosome 6. TaHd1‐2 harbored a 63‐bp deletion at the promoter region containing the GATA‐1 box, and consequently, we detected no subsequent transcript. The TaHd1‐1 genomic clone was introduced to a rice line deficient in Hd1 function. Transgenic plants complemented the functions of rice Hd1: they promoted heading under short‐day (SD) conditions and delayed it under long‐day (LD)/natural conditions, indicating that Hd1 proteins from SD and LD plants share common structures and functions.
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The disruption of eight novel genes was realized in two genetic backgrounds. Among these open reading frames, NO333, NO348 and NO364 presented homologies with other proteins of yeast or other organisms, whereas NO320, NO325, NO339, NO384 and NO388 showed no similarity with any protein. Tetrad analysis of heterozygous deletant strains revealed that NO348, NO364 and NO388 are essential genes for vegetative growth, whereas NO320, NO325, NO333, NO339 and NO384 are non-essential. Basic phenotypic analyses of the non-lethal deletant strains as suggested in the six-pack B0 programme did not reveal any significant differences between parental and mutant strains. © 1998 John Wiley & Sons, Ltd.
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Journal Article A BamHI polymorphism in the human EVI2A gene (human homolog of the murine gene Evi-2) Get access W. Xu, W. Xu * CRC Human Cancer Genetics Group, Department of Pathology, University of CambridgeUK * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Liu, L. Liu CRC Human Cancer Genetics Group, Department of Pathology, University of CambridgeUK Search for other works by this author on: Oxford Academic PubMed Google Scholar B.A.J. Ponder B.A.J. Ponder CRC Human Cancer Genetics Group, Department of Pathology, University of CambridgeUK Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 9, 11 May 1991, Page 2520, https://doi.org/10.1093/nar/19.9.2520 Published: 11 May 1991
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Gene rearrangement
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In order to identify genes involved in pathogenicity, we compared the closely related species Globodera pallida (GP) and Globodera “mexicana” (GM) that have different host ranges and are able to produce viable and fertile hybrids. Three pioneer genes were previously identified as differentially expressed between GP and GM: GPLIA7 and GPLIB3 were found to be more highly expressed in GP, whereas GMLIVG9 was found more highly expressed in GM. In this study, we showed that Ia7 and IVg9 genes probably encode products secreted by the subventral oesophageal glands and the dorsal oesophageal gland, respectively. No Blast homolog was found in the databases, but a metridin-like ShK (Stichodactyla helianthus) toxin domain was identified in the Ia7 sequence. Analysis of the full-length sequences of these 2 genes between GP and GM revealed a high level of interspecies variability (8% for the Ia7 transcript and 17% for the IVg9 transcript) and a high proportion (90%) of nonsynonymous mutations among the substitutions observed. This suggested that these 2 pioneer genes are under strong diversifying selection pressures and therefore may be involved in pathogenicity. Further investigations of the sequence polymorphism of Ia7 and IVg9 genes were conducted in GP × GM hybrid lines that were selected in laboratory conditions for their different ability to develop on potato and black nightshade. As similar sequences were obtained for all the hybrid lines tested independently of their pathogenicity status, no correlation could be established between IA7 and IVG9 amino acid changes and the host range differences observed between GP and GM.
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