scholarly journals TECHNIQUES FOR MANIPULATING CHROMOSOMAL REARRANGEMENTS AND THEIR APPLICATION TO DROSOPHILA MELANOGASTER. II. TRANSLOCATIONS

Genetics ◽  
1984 ◽  
Vol 108 (3) ◽  
pp. 573-587
Author(s):  
Loring Craymer
Keyword(s):  
Tandem Duplication ◽  
Gene Dosage ◽  
Chromosomal Rearrangements ◽  
Region Of Interest ◽  
Reciprocal Translocations ◽  
The Third ◽  
Translocation Breakpoints ◽  
Inversion Breakpoints ◽  
Derivatives Of ◽  
Tandem Duplications

ABSTRACT Translocations have long been valued for their segregational properties. This paper extends the utility of translocations by considering recombinational derivatives of pairs of simple reciprocal translocations. Three major derivative structures are noted. One of these derivatives is suitable for use in half-tetrad experiments. A second should find use in recombining markers with translocation breakpoints. The third is an insertional-tandem duplication: it has a section of one chromosome inserted into a heterologue with a section of the latter chromosome tandemly repeated about the breaks of the insert. All of these structures are contained in "constellations" of chromosomes that regularly segregate aneuploid-1 products (informationally equivalent to nonrecombinant adjacent-1 segregants) for one of the parental translocations but do not segregate euploid products. This is in contrast to the parental T  1/T  2 constellations which segregate euploid products but not aneuploid-1 products. Methods are described for selecting translocation recombinants on the basis of this dichotomy. Several examples of translocation recombinants have been recovered with these techniques, and the recombination frequencies seem to be consistent with those observed for crossovers between inversion breakpoints. Recombinant chromosomes tend to disjoin, but it is observed that the tendency may vary according to the region involved in the recombination, and it is suggested that this difference reflects a difference in chiasmata terminalization times. Special consideration is given to insertional-tandem duplications. Large insertional-tandem duplications are useful in cytogenetic screens. Small insertional-tandem duplications are useful in gene dosage studies and other experiments that require an insert from one chromosome to another. Large duplications can be deleted to form small duplications. To generate a small insert for a specified region, it is only necessary to have one translocation with a breakpoint flanking the region of interest. The second translocation can have a breakpoint quite far from the region: an insertional-tandem duplication containing the region that has one closely flanking breakpoint can be deleted to create a smaller duplication that has two closely flanking breakpoints.

scholarly journals TECHNIQUES FOR MANIPULATING CHROMOSOMAL REARRANGEMENTS AND THEIR APPLICATION TO DROSOPHILA MELANOGASTER. I. PERICENTRIC INVERSIONS

Genetics ◽  
1981 ◽  
Vol 99 (1) ◽  
pp. 75-97
Author(s):  
Loring Craymer
Keyword(s):  
Drosophila Melanogaster ◽  
Tandem Duplication ◽  
Chromosomal Rearrangements ◽  
Pericentric Inversions ◽  
Derivatives Of ◽  
Tandem Duplications ◽  
Dominant Lethality ◽  
Inversion Loop

ABSTRACT Techniques have been developed for manipulating pericentric inversions in Drosophila that are based on the lethality of grossly aneuploid zygotes and the existence of recombinationally interconvertible genotypes for any heterozygous inversion complex: males of some of these genotypes will produce only aneuploid sperm, which can be used to rescue complementary aneuploid ova and selectively recover recombinational derivatives of inversions. Markers can be recombined into inversions through a sequence of selected single exchanges, and a novel type of duplication can be synthesized from overlapping inversions that has the characteristics of both insertional and tandem duplications; there are also applications to half-tetrad analyses.——Two cytogenetic screens are developed: (1) the dominant lethality of a large insertional-tandem duplication can be reverted by deletional events that give rise to net deficiencies or duplications, and (2) deficiencies and tandem duplications in proximal regions can be selectively recovered as the results of unequal exchanges within an inversion loop. Recombinants have been recovered between breakpoints separated by distances of as little as fifty bands, arguing against the existence of some small number of sites necessary for the initiation of recombinational pairing. In several instances, hyperploids for four to six numbered divisions were observed to be fertile in both sexes.

Identification of Candidate Oncogenes and Chromosomal Breakpoint Sequencing By Targeted Locus Amplification in T-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1409-1409
Author(s):  
Eric M Vroegindeweij ◽  
Tim Lammens ◽  
Erik Splinter ◽  
Anne Uyttebroeck ◽  
Kirsten Canté-Barrett ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Transcriptional Control ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Rearrangements ◽  
Chromosomal Translocations ◽  
The Third ◽  
P Gene ◽  
Translocation Breakpoints ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Background: T-cell acute lymphoblastic leukemia is characterized by clonal and mutual exclusive chromosomal rearrangements that recurrently activate TAL1, LMO2, TLX1, NKX2-1, TLX3, HOXA or MEF2C oncogenes. Most of these translocations or chromosomal rearrangements occur as erroneous D-J or V-DJ rearrangement attempts of T-cell receptor beta (TCRB) or TCR alpha/delta (TCRAD) genes, mostly positioning oncogenes under the transcriptional control of TCR enhancer elements. Alternatively, oncogenes can also be activated as consequence of BCL11B chromosomal rearrangements. Although many oncogenes are known in T-ALL, the driving oncogenic lesion in particular T-ALL cases remains unknown. Aims: In this study, we aimed to clone reciprocal breakpoint sequences to elucidate cellular mechanisms that lead to recurrent BCL11B -TLX3 chromosomal translocations. Moreover, we want to identify oncogene candidates in various T-ALL patient samples with BCL11B-, TCRB- or TCRAD-translocations for which the candidate oncogene so far has not been identified. Methods: We used Targeted Locus Amplification procedure, a recently developed method that relies on the crosslinking of DNA in live cells, DNA digestion and re-ligation to allow formation of circular DNA ligation fragments and inverted polymerase chain reaction amplification from specific view-point loci. Amplified DNA fragments are sequenced by next generation sequencing, allowing sequence identification in a region covering 2MB around selected regions of interest, including TLX3, TLX1, TAL1, LMO2, BCL11B, TCRAD (TRAJ61), TCRB (TCRBC2) Results: TLA was successfully performed on 10 T-ALL patients having FISH validated TAL1 translocations (2 patients), LMO2 translocations (3 patients), TLX3 translocations (3 patients), TLX1 translocations (2 patients) or an inversion targeting NKX2.1 (1 patient). Analysis of both TAL1 translocated cases revealed a TAL1-TCRAD genomic fusion due to a classical t(1;14)(q32;q11) in 1 patient, but surprisingly reveal a TAL1-TCF7 genomic fusion due to a t(1;5)(q32;q31.1) chromosomal translocation in the second patient. For the LMO2 translocated cases, two patients showed classical LMO2-TCRAD (t(11;14)(p13;q11)) or LMO2-TCRB (t(7;11)(q35;p13) translocations, whereas the third patient presented with an unusual LMO2-BCL11B genomic fusion due to a t(11;14)(p13;q32). Two out of 3 TLX3-translocated patients had classical t(5;14)(q35;q32) translocations, whereas the TLX3 gene in the third patient was rearranged to the calcyphosine-like gene (CAPSL, which flanks the IL7Ra gene) on chromosomal 5p13.2 due to a t(5;5)( p13.2;q35) or an inv(5). One patient had an inversion on chromosome 14, i.e. inv(14)(q11;q13), that brings the NKX2.1 oncogene under the transcriptional control of the TCRAD enhancer. Finally, one TLX1-rearranged patient had a classical TLX1-TCRAD translocation, whereas the other presented with a chromosomal inversion involving the chromosomal band 10q24 (which included TLX1), but also revealed a novel translocation involving the centromere protein P gene (CENPP) on chromosome 9q22.31 with the TCRAD locus. Summary/Conclusions: Targeted Locus Amplification identification of chromosomal rearrangements and genomic breakpoint sequences reveals novel complex translocations in 3 out of 10 T-ALL cases analyzed thus far, indicating higher complexity of chromosomal translocations of known T-ALL oncogenes as thus far anticipated. It further proved a useful tool to identify novel translocation partners from various loci such as the TCR or BCL11B genes that are recurrently involved in these chromosomal rearrangements in T-ALL. Cloning of molecular translocation breakpoints of diagnostic T-ALL patient samples may further provide excellent minimal residual disease markers for disease monitoring during the course of treatment. Disclosures Splinter: Cergentis BV: Employment. van Min:Cergentis BV: Employment.

scholarly journals EVIDENCE FOR DUPLICATION AND DIVERGENCE OF THE STRUCTURAL GENE FOR PHOSPHOGLUCOISOMERASE IN DIPLOID SPECIES OF CLARKIA

Genetics ◽  
1977 ◽  
Vol 86 (2) ◽  
pp. 289-307
Author(s):  
L D Gottlieb
Keyword(s):  
Chromosomal Rearrangements ◽  
Diploid Species ◽  
Duplicate Gene ◽  
Structural Similarity ◽  
Reciprocal Translocations ◽  
Electrophoretic Variants ◽  
Ancestral Gene ◽  
The Third ◽  
Michaelis Constants ◽  
Intermediate Value

ABSTRACT Formal genetic analysis of the mode of inheritance of the electrophoretic phenotypes for phosphoglucoisomerase (PGI) in the annual plants Clarkia rubicunda and C. xantiana showed that these diploid species have two and three genes, respectively, that specify PGI subunits. Electrophoretic examination of seven other diploid species of Clarkia revealed that species assigned to ancestral sections in the current taxonomy have two PGI genes, whereas more specialized species have three PGI genes. Together with evidence that diploid species in two closely related genera have two PGI genes, this suggests the third PGI gene arose within Clarkia. Intergenic heterodimers are formed between polypeptides specified by the third gene and one of the other PGI genes, indicating they have a high degree of structural similarity. The combined genetic, biochemical, and phylogenetic evidence suggests that the third PGI gene resulted from a process of gene duplication. The apparent Michaelis constants (F6P to G6P) of the most common electrophoretic variants of the ancestral gene in C. xantiana and in C. rubicunda are closely similar, but that of the duplicate enzyme is much higher. The intergenic heteromer has an intermediate value. Four alleles have been identified for the duplicate PGI gene in C. xantiana, including a null allele which eliminates the activity of its product. This allele is one of the few examples of a "silenced" duplicate gene. The ancestral and duplicate genes assort independently in C. xantiana. In conjunction with the substantial chromosomal rearrangements that characterize species of Clarkia, this may mean that the duplicate PGI marks a duplicated chromosomal segment that originated from a cross between partially overlapping reciprocal translocations rather than from unequal crossing over.

scholarly journals Tandem duplications lead to novel expression patterns through exon shuffling in D. yakuba

2016 ◽  
Author(s):  
Rebekah L. Rogers ◽  
Ling Shao ◽  
Kevin R. Thornton
Keyword(s):  
Gene Expression ◽  
Copy Number ◽  
Tandem Duplication ◽  
De Novo ◽  
Gene Dosage ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Gene Duplications ◽  
Gene Structures ◽  
Tandem Duplications

AbstractOne common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. Here, we use genome wide RNA-seq data from a population sample of Drosophila yakuba to test this ‘gene dosage’ hypothesis. We observe little evidence of expression changes in response to whole transcript duplication capturing 5ʹ and 3ʹ UTRs. Among whole gene duplications, we observe evidence that dosage sharing across copies is likely to be common. The lack of expression changes after whole gene duplication suggests that the majority of genes are subject to tight regulatory control and therefore not sensitive to changes in gene copy number. Rather, we observe changes in expression level due to both shuffling of regulatory elements and the creation of chimeric structures via tandem duplication. Additionally, we observe 30 de novo gene structures arising from tandem duplications, 23 of which form with expression in the testes. Thus, the value of tandem duplications is likely to be more intricate than simple changes in gene dosage. The common regulatory effects from chimeric gene formation after tandem duplication may explain their contribution to genome evolution.Author SummaryThe enclosed work shows that whole gene duplications rarely affect gene expression, in contrast to widely held views that the adaptive value of duplicate genes is related to additive changes in gene expression due to gene copy number. We further explain how tandem duplications that create shuffled gene structures can force upregulation of gene sequences, de novo gene creation, and multifold changes in transcript levels.These results show that tandem duplications can produce new genes that are a source of immediate novelty associated with more extreme expression changes than previously suggested by theory. Further, these gene expression changes are a potential source of both beneficial and pathogenic mutations, immediately relevant to clinical and medical genetics in humans and other metazoans.

Investigations on skeletal growth zones via bone scans as base of determination of optimal time for surgery in mandibular asymmetry

2000 ◽  
Vol 39 (05) ◽  
pp. 121-126 ◽  
Author(s):  
R. Werz ◽  
P. Reuland
Keyword(s):  
Bone Growth ◽  
Region Of Interest ◽  
Tracer Uptake ◽  
Optimal Time ◽  
Mandibular Bone ◽  
The Third ◽  
Mandibular Asymmetry ◽  
Bone Scans ◽  
Epiphyseal Plates

Summary Aim of the study was to find out wether there is a common stop of growth of mandibular bone, so that no individual determination of the optimal time for surgery in patients with asymmetric mandibular bone growth is needed. As there are no epiphyseal plates in the mandibular bone, stop of growth cannot be determined on X-ray films. Methods: Bone scans of 731 patients [687 patients (324 male, 363 female) under 39 y for exact determination of end of growth and 44 (21 male, 23 female) patients over 40 y for evaluation of nongrowth dependant differences in tracer uptake] were reviewed for the study. All the patients were examined 3 hours after injection of 99mTc-DPD. Tracer uptake was measured by region of interest technique in different points of the mandibular bone and in several epiphyseal plates of extremities. Results: Tracer uptake in different epiphyseal plates of the extremities shows strong variation with age and good correlation with reported data of bone growth and closure of the epiphyseal plates. The relative maximum of bone activity is smaller in mandibular bone than in epiphyseal plates, which show well defined peaks, ending at 15-18 years in females and at 18-21 years in males. In contrast, mandibular bone shows no well defined end of growing but a gradually reduction of bone activity which remains higher than bone activity in epiphyseal plates over several years. Conclusion: No well defined end of growth of mandibular bone exists. The optimal age for surgery of asymmetric mandibular bone growth is not before the middle of the third decade of life, bone scans performed earlier for determination of bone growth can be omitted. Bone scans performed at the middle of the third decade of life help to optimize the time of surgical intervention.

scholarly journals Identification, Expression and Evolution of Short-Chain Dehydrogenases/Reductases in Nile Tilapia (Oreochromis niloticus)

2021 ◽  
Vol 22 (8) ◽  
pp. 4201
Author(s):  
Shuai Zhang ◽  
Lang Xie ◽  
Shuqing Zheng ◽  
Baoyue Lu ◽  
Wenjing Tao ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Tandem Duplication ◽  
Developmental Stages ◽  
Short Chain ◽  
Sexually Dimorphic ◽  
Physiological Processes ◽  
Genome Wide ◽  
Nile Tilapia Oreochromis Niloticus ◽  
Tandem Duplications

The short-chain dehydrogenases/reductases (SDR) superfamily is involved in multiple physiological processes. In this study, genome-wide identification and comprehensive analysis of SDR superfamily were carried out in 29 animal species based on the latest genome databases. Overall, the number of SDR genes in animals increased with whole genome duplication (WGD), suggesting the expansion of SDRs during evolution, especially in 3R-WGD and polyploidization of teleosts. Phylogenetic analysis indicated that vertebrates SDRs were clustered into five categories: classical, extended, undefined, atypical, and complex. Moreover, tandem duplication of hpgd-a, rdh8b and dhrs13 was observed in teleosts analyzed. Additionally, tandem duplications of dhrs11-a, dhrs7a, hsd11b1b, and cbr1-a were observed in all cichlids analyzed, and tandem duplication of rdh10-b was observed in tilapiines. Transcriptome analysis of adult fish revealed that 93 SDRs were expressed in more than one tissue and 5 in one tissue only. Transcriptome analysis of gonads from different developmental stages showed that expression of 17 SDRs were sexually dimorphic with 11 higher in ovary and 6 higher in testis. The sexually dimorphic expressions of these SDRs were confirmed by in situ hybridization (ISH) and qPCR, indicating their possible roles in steroidogenesis and gonadal differentiation. Taken together, the identification and the expression data obtained in this study contribute to a better understanding of SDR superfamily evolution and functions in teleosts.

scholarly journals Third derivatives of the integrable part of an asteroid Hamiltonian

2007 ◽  
pp. 53-60 ◽  
Author(s):  
R. Pavlovic
Keyword(s):  
Third Order ◽  
Geometrical Condition ◽  
The Third ◽  
Derivatives Of ◽  
Quasi Convexity ◽  
Explicit Expressions

To apply the theorem of Nekhoroshev (1977) to asteroids, one first has to check whether a necessary geometrical condition is fulfilled: either convexity, or quasi-convexity, or only a 3-jet non-degeneracy. This requires computation of the derivatives of the integrable part of the corresponding Hamiltonian up to the third order over actions and a thorough analysis of their properties. In this paper we describe in detail the procedure of derivation and we give explicit expressions for the obtained derivatives. .

scholarly journals HIGH RATES OF OCCURRENCE OF SPONTANEOUS CHROMOSOME ABERRATIONS IN DROSOPHILA MELANOGASTER

Genetics ◽  
1976 ◽  
Vol 83 (2) ◽  
pp. 409-422
Author(s):  
Osamu Yamaguchi ◽  
Ricardo A Cardellino ◽  
Terumi Mukai
Keyword(s):  
Chromosome Aberrations ◽  
Gene Arrangement ◽  
Reciprocal Translocations ◽  
Lethal Effects ◽  
Recessive Lethal ◽  
The Third ◽  
Lethal Mutations ◽  
Pericentric Inversions ◽  
Break Points ◽  
Spontaneous Chromosome

ABSTRACT Spontaneous mutations were accumulated for 40 generations in 140 unrelated second chromosomes with the standard gene arrangement. These were extracted from the same population by using the marked inversion technique, and the following findings were obtained: (1) In 42 out of the 140 chromosome lines, chromosome aberrations were detected by examining the salivary gland chromosomes: 40 paracentric and 15 pericentric inversions, 2 reciprocal translocations between the second and the third chromosomes, and 6 transpositions. (2) In 63 out of the 90 originally lethal-free lines, recessive lethal mutations occurred. (3) There were only 3 lines that acquired chromosome aberrations (inversions) with no lethal effects in the homozygous condition. (4) In a comparison of these results with those of the (CH), (PQ), and (RT) chromosomes in which no chromosome aberrations occurred after accumulating mutations for 22058 chromosome·generations (Yamaguchi and Mukai 1974), it was concluded that some of these 140 chromosomes carried a kind of mutator. (5) The frequency of mutator-carrying chromosome lines was estimated to be 0.66 on the basis of the distribution of the break-points on the chromosome lines and the frequency of lines that acquired neither recessive lethal mutations nor chromosome aberrations. Thus, the average number of breaks per mutator-carrying chromosome was estimated to be about 0.19/generation. On the basis of these estimates, the nature of the mutator factor was discussed.

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