Molecular Genetic Analysis of Drosophila eyes absent Mutants Reveals an Eye Enhancer Element

Abstract The eyes absent (eya) gene is critical for normal eye development in Drosophila and is highly conserved to vertebrates. To define regions of the gene critical for eye function, we have defined the mutations in the four viable eya alleles. Two of these mutations are eye specific and undergo transvection with other mutations in the gene. These were found to be deletion mutations that remove regulatory sequence critical for eye cell expression of the gene. Two other viable alleles cause a reduced eye phenotype and affect the function of the gene in additional tissues, such as the ocelli. These mutations were found to be insertion mutations of different transposable elements within the 5′ UTR of the transcript. Detailed analysis of one of these revealed that the transposable element has become subject to regulation by eye enhancer sequences of the eya gene, disrupting normal expression of EYA in the eye. More extended analysis of the deletion region in the eye-specific alleles indicated that the deleted region defines an enhancer that activates gene expression in eye progenitor cells. This enhancer is responsive to ectopic expression of the eyeless gene. This analysis has defined a critical regulatory region required for proper eye expression of the eya gene.

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Molecular Genetic Analysis of Nucleotide Polymorphisms Associated with Ethambutol Resistance in Human Isolates ofMycobacterium tuberculosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.2.326-336.2000 ◽

2000 ◽

Vol 44 (2) ◽

pp. 326-336 ◽

Cited By ~ 154

Author(s):

Srinivas V. Ramaswamy ◽

Amol G. Amin ◽

Servet Göksel ◽

Charles E. Stager ◽

Shu-Jun Dou ◽

...

Keyword(s):

Amino Acid ◽

Single Gene ◽

Molecular Genetic ◽

Regulatory Region ◽

Amino Acid Replacement ◽

Molecular Genetic Analysis ◽

Central Component ◽

Nucleotide Polymorphisms ◽

Molecular Change

ABSTRACT Ethambutol (EMB) is a central component of drug regimens used worldwide for the treatment of tuberculosis. To gain insight into the molecular genetic basis of EMB resistance, approximately 2 Mb of five chromosomal regions with 12 genes in 75 epidemiologically unassociated EMB-resistant and 33 EMB-susceptible Mycobacterium tuberculosis strains isolated from human patients were sequenced. Seventy-six percent of EMB-resistant organisms had an amino acid replacement or other molecular change not found in EMB-susceptible strains. Thirty-eight (51%) EMB-resistant isolates had a resistance-associated mutation in only 1 of the 12 genes sequenced. Nineteen EMB-resistant isolates had resistance-associated nucleotide changes that conferred amino acid replacements or upstream potential regulatory region mutations in two or more genes. Most isolates (68%) with resistance-associated mutations in a single gene had nucleotide changes in embB, a gene encoding an arabinosyltransferase involved in cell wall biosynthesis. The majority of these mutations resulted in amino acid replacements at position 306 or 406 of EmbB. Resistance-associated mutations were also identified in several genes recently shown to be upregulated in response to exposure of M. tuberculosis to EMB in vitro, including genes in theiniA operon. Approximately one-fourth of the organisms studied lacked mutations inferred to participate in EMB resistance, a result indicating that one or more genes that mediate resistance to this drug remain to be discovered. Taken together, the results indicate that there are multiple molecular pathways to the EMB resistance phenotype.

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The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma

Blood ◽

10.1182/blood.v95.8.2719.008k15_2719_2721 ◽

2000 ◽

Vol 95 (8) ◽

pp. 2719-2721 ◽

Cited By ~ 3

Author(s):

Yoshitaka Hosokawa ◽

Yumiko Maeda ◽

Ryo Ichinohasama ◽

Ikuo Miura ◽

Masafumi Taniwaki ◽

...

Keyword(s):

B Cell ◽

Molecular Genetic ◽

Regulatory Region ◽

B Cell Lymphoma ◽

Molecular Genetic Analysis ◽

B Cell Differentiation ◽

Polymerase Chain ◽

Large B Cell

The BCL6 gene, isolated from the breakpoints of 3q27-associated chromosomal translocations, has been implicated in diffuse large B-cell lymphomas (DLBL). Here we describe the molecular characterization of novel t(3;7)(q27;p12) translocations in 2 patients with DLBL. Molecular genetic analysis of the breakpoint area involving BCL6 revealed the presence of the Ikaros gene, a central regulator of lymphoid differentiation that had been mapped to human chromosome 7 band p13-p11.1. As a molecular consequence of the translocation, the 5′ regulatory region of the BCL6 gene was replaced by the putative 5′ regulatory region of theIkaros gene, probably leading to deregulated expression of theBCL6 gene throughout B-cell differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) analyses of a patient sample established that the t(3;7)(q27;p12) results in fusion of the Ikaros andBCL6 genes. This study provides the first evidence that the Ikaros gene is rearranged in human hematopoietic malignant disorders.

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The Ikaros gene, a central regulator of lymphoid differentiation, fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in a patient with diffuse large B-cell lymphoma

Blood ◽

10.1182/blood.v95.8.2719 ◽

2000 ◽

Vol 95 (8) ◽

pp. 2719-2721 ◽

Cited By ~ 29

Author(s):

Yoshitaka Hosokawa ◽

Yumiko Maeda ◽

Ryo Ichinohasama ◽

Ikuo Miura ◽

Masafumi Taniwaki ◽

...

Keyword(s):

B Cell ◽

Molecular Genetic ◽

Regulatory Region ◽

B Cell Lymphoma ◽

Molecular Genetic Analysis ◽

B Cell Differentiation ◽

Polymerase Chain ◽

Large B Cell

Abstract The BCL6 gene, isolated from the breakpoints of 3q27-associated chromosomal translocations, has been implicated in diffuse large B-cell lymphomas (DLBL). Here we describe the molecular characterization of novel t(3;7)(q27;p12) translocations in 2 patients with DLBL. Molecular genetic analysis of the breakpoint area involving BCL6 revealed the presence of the Ikaros gene, a central regulator of lymphoid differentiation that had been mapped to human chromosome 7 band p13-p11.1. As a molecular consequence of the translocation, the 5′ regulatory region of the BCL6 gene was replaced by the putative 5′ regulatory region of theIkaros gene, probably leading to deregulated expression of theBCL6 gene throughout B-cell differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) analyses of a patient sample established that the t(3;7)(q27;p12) results in fusion of the Ikaros andBCL6 genes. This study provides the first evidence that the Ikaros gene is rearranged in human hematopoietic malignant disorders.

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Molecular Analysis of Drosophilaeyes absentMutants Reveals Features of the Conserved Eya Domain

Genetics ◽

10.1093/genetics/155.2.709 ◽

2000 ◽

Vol 155 (2) ◽

pp. 709-720 ◽

Cited By ~ 2

Author(s):

Quang T Bui ◽

John E Zimmerman ◽

Haixi Liu ◽

Nancy M Bonini

Keyword(s):

Protein Sequence ◽

Molecular Genetic ◽

Molecular Genetic Analysis ◽

Special Importance ◽

Missense Mutations ◽

Eyes Absent ◽

Sine Oculis ◽

Eye Formation

AbstractThe eyes absent (eya) gene is critical to eye formation in Drosophila; upon loss of eya function, eye progenitor cells die by programmed cell death. Moreover, ectopic eya expression directs eye formation, and eya functionally synergizes in vivo and physically interacts in vitro with two other genes of eye development, sine oculis and dachshund. The Eya protein sequence, while highly conserved to vertebrates, is novel. To define amino acids critical to the function of the Eya protein, we have sequenced eya alleles. These mutations have revealed that loss of the entire Eya Domain is null for eya activity, but that alleles with truncations within the Eya Domain display partial function. We then extended the molecular genetic analysis to interactions within the Eya Domain. This analysis has revealed regions of special importance to interaction with Sine Oculis or Dachshund. Select eya missense mutations within the Eya Domain diminished the interactions with Sine Oculis or Dachshund. Taken together, these data suggest that the conserved Eya Domain is critical for eya activity and may have functional subregions within it.

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An evolutionarily conserved cis-regulatory element of Nkx3.2 contributes to early jaw joint morphology in zebrafish

10.1101/2021.11.26.470082 ◽

2021 ◽

Author(s):

Jake Leyhr ◽

Laura Waldmann ◽

Beata Filipek-Górniok ◽

Hanqing Zhang ◽

Amin Allalou ◽

...

Keyword(s):

Regulatory Element ◽

Regulatory Sequence ◽

Enhancer Element ◽

Functional Conservation ◽

Evolutionarily Conserved ◽

Joint Deformation ◽

Jaw Joint ◽

Enhancer Sequences ◽

High Degree

The acquisition of movable jaws was a major event during vertebrate evolution. The role of NK3 homeobox 2 (Nkx3.2) transcription factor in patterning the primary jaw joint of gnathostomes (jawed vertebrates) is well known, however knowledge about its regulatory mechanism is lacking. In this study, we report a proximal enhancer element of Nkx3.2 that is deeply conserved in gnathostomes but undetectable in the jawless hagfish. This enhancer is active in the developing jaw joint region of the zebrafish Danio rerio, and was thus designated as jaw joint regulatory sequence 1 (JRS1). We further show that JRS1 enhancer sequences from a range of gnathostome species, including a chondrichthyan and mammals, have the same activity in the jaw joint as the native zebrafish enhancer, indicating a high degree of functional conservation despite the divergence of cartilaginous and bony fish lineages or the transition of the primary jaw joint into the middle ear of mammals. Finally, we show that deletion of JRS1 from the zebrafish genome using CRISPR/Cas9 leads to a transient jaw joint deformation and partial fusion. Emergence of this Nkx3.2 enhancer in early gnathostomes may have contributed to the origin and shaping of the articulating surfaces of vertebrate jaws.

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Molecular Characterization and Genetic Diversity Study in F3 Population of Rice

Progressive Agriculture ◽

10.3329/pa.v20i1-2.16839 ◽

2013 ◽

Vol 20 (1-2) ◽

pp. 1-8

Author(s):

MM Rahman ◽

L Rahman ◽

SN Begum ◽

F Nur

Keyword(s):

Genetic Distance ◽

Gene Diversity ◽

Random Amplified Polymorphic Dna ◽

Molecular Genetic ◽

Molecular Genetic Analysis ◽

Polymorphic Loci ◽

Rice Genotypes ◽

High Level ◽

Genetic Diversity Study ◽

Diversity Study

Random Amplified Polymorphic DNA (RAPD) assay was initiated for molecular genetic analysis among 13 F3 rice lines and their parents. Four out of 15 decamer random primers were used to amplify genomic DNA and the primers yielded a total of 41 RAPD markers of which 37 were considered as polymorphic with a mean of 9.25 bands per primer. The percentage of polymorphic loci was 90.24. The highest percentage of polymorphic loci (14.63) and gene diversity (0.0714) was observed in 05-6 F3 line and the lowest polymorphic loci (0.00) and gene diversity (0.00) was found in 05-12 and 05-15 F3 lines. So, relatively high level of genetic variation was found in 05-6 F3 line and it was genetically more diverse compared to others. The average co-efficient of gene differentiation (GST) and gene flow (Nm) values across all the loci were 0.8689 and 0.0755, respectively. The UPGMA dendrogram based on the Neis genetic distance differentiated the rice genotypes into two main clusters: PNR-519, 05-19, 05-14, 05-12 and 05-17 grouped in cluster 1. On the other hand, Baradhan, 05-9, 05-13, 05-11, 05-5, 05-6, 05-1, 05-4, 05-15 and 05-25 were grouped in cluster 2. The highest genetic distance (0.586) was found between 05-4 and 05-17 F3 lines and they remain in different cluster.DOI: http://dx.doi.org/10.3329/pa.v20i1-2.16839 Progress. Agric. 20(1 & 2): 1 8, 2009

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Diagnosis and Management of Cardiomyopathies – A Focus on Genetics, Cardiac Magnetic Resonance and Clinical Features

European Cardiology Review ◽

10.15420/ecr.2011.7.3.225 ◽

2011 ◽

Vol 7 (3) ◽

pp. 225

Author(s):

Gianfranco Sinagra ◽

Michele Moretti ◽

Giancarlo Vitrella ◽

Marco Merlo ◽

Rossana Bussani ◽

...

Keyword(s):

Clinical Practice ◽

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Imaging Techniques ◽

Molecular Genetic ◽

Molecular Genetic Analysis ◽

Routine Clinical Practice ◽

Clinical Approach ◽

Diagnosis And Management ◽

Made In

In recent years, outstanding progress has been made in the diagnosis and treatment of cardiomyopathies. Genetics is emerging as a primary point in the diagnosis and management of these diseases. However, molecular genetic analyses are not yet included in routine clinical practice, mainly because of their elevated costs and execution time. A patient-based and patient-oriented clinical approach, coupled with new imaging techniques such as cardiac magnetic resonance, can be of great help in selecting patients for molecular genetic analysis and is crucial for a better characterisation of these diseases. This article will specifically address clinical, magnetic resonance and genetic aspects of the diagnosis and management of cardiomyopathies.

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