Mapping and genomic characterization of the gene encoding diacylglycerol kinase γ ( DAGK3 ): assessment of its role in dominant optic atrophy ( OPA1 )

Abstract

The family of diacylglycerol kinases (DAGKs) is known to play an important role in signal transduction linked to phospholipid turnover. In the fruitfly Drosophila melanogaster, a human DAGK ortholog, DGK2, was shown to underlie the phenotype of the visual mutant retinal degeneration A (rdgA). Previously, the gene encoding a novel member of the human DAGK family, termed DAGK3, was cloned and demonstrated to be abundantly expressed in the human retina. Based on these findings we reasoned that DAGK3 might be an excellent candidate gene for a human eye disease. In the present study, we report the genomic organization of the human DAGK3 gene, which spans over 30 kb of genomic DNA interrupted by 23 introns. In addition, we have mapped the gene locus by fluorescence in situ hybridization to 3q27-28, overlapping the chromosomal region known to contain the gene underlying dominant optic atrophy (OPA1), the most common form of hereditary atrophy of the optic nerve. Mutational analysis of the entire coding region of DAGK3 in 19 unrelated German OPA1 patients has not revealed any disease-causing mutations, therefore excluding DAGK3 as a major cause underlying OPA1.

A New Locus for a Dominant Form of Multinodular Goiter on 3q26.1-q26.3

“…For mutational analysis, amplification of each of 24 exons of DAGK3 gene was conducted using PCR primer sets as reported previously (14). Direct sequencing was conducted in a conventional manner.…”

A New Locus for a Dominant Form of Multinodular Goiter on 3q26.1-q26.3

“…For mutational analysis, amplification of each of 24 exons of DAGK3 gene was conducted using PCR primer sets as reported previously (14). Direct sequencing was conducted in a conventional manner.…”

Molecular Biologic Characteristics of Seven New Cell Lines of Squamous Cell Carcinomas of the Head and Neck and Comparison to Fresh Tumor Tissue

“…In this region, genes which have some impact on signal transduction are located, e.g. the diacylglycerol kinase 3 (DAGK3) gene, the PIKCA3 gene, and cytokins like the thrombopoietin gene [38, 39, 40, 41]. Furthermore, overrepresentations on 3q27–28 are common cytogenetic findings in severe dysplasias/carcinoma in situ, which may be a key event occurring early during carcinogenesis [42, 43].…”

Comparative Analysis of Gene Expression for Convergent Evolution of Camera Eye Between Octopus and Human

“…Moreover, we found that five out of the 14 genes were certainly involved in the function of the camera eyes of humans and octopuses. For example, diacylglycerol kinase ␥, which is expressed in the rod outer segment of the retina, was found in humans and octopuses, but not in the invertebrates examined except octopus (Stohr et al 1999). For another example, dihydroxyacetonephosphate acyltransferase is the peroxisomal key enzyme of plasmalogen biosynthesis in eye-lens epithelial cells (Thai et al 1999).…”

A New Locus for a Dominant Form of Multinodular Goiter on 3q26.1-q26.3

“…For mutational analysis, amplification of each of 24 exons of DAGK3 gene was conducted using PCR primer sets as reported previously (14). Direct sequencing was conducted in a conventional manner.…”

Molecular Biologic Characteristics of Seven New Cell Lines of Squamous Cell Carcinomas of the Head and Neck and Comparison to Fresh Tumor Tissue

“…In this region, genes which have some impact on signal transduction are located, e.g. the diacylglycerol kinase 3 (DAGK3) gene, the PIKCA3 gene, and cytokins like the thrombopoietin gene [38, 39, 40, 41]. Furthermore, overrepresentations on 3q27–28 are common cytogenetic findings in severe dysplasias/carcinoma in situ, which may be a key event occurring early during carcinogenesis [42, 43].…”

Comparative Analysis of Gene Expression for Convergent Evolution of Camera Eye Between Octopus and Human

“…Moreover, we found that five out of the 14 genes were certainly involved in the function of the camera eyes of humans and octopuses. For example, diacylglycerol kinase ␥, which is expressed in the rod outer segment of the retina, was found in humans and octopuses, but not in the invertebrates examined except octopus (Stohr et al 1999). For another example, dihydroxyacetonephosphate acyltransferase is the peroxisomal key enzyme of plasmalogen biosynthesis in eye-lens epithelial cells (Thai et al 1999).…”

A New Locus for a Dominant Form of Multinodular Goiter on 3q26.1-q26.3

“…For mutational analysis, amplification of each of 24 exons of DAGK3 gene was conducted using PCR primer sets as reported previously (14). Direct sequencing was conducted in a conventional manner.…”

Molecular Biologic Characteristics of Seven New Cell Lines of Squamous Cell Carcinomas of the Head and Neck and Comparison to Fresh Tumor Tissue

“…In this region, genes which have some impact on signal transduction are located, e.g. the diacylglycerol kinase 3 (DAGK3) gene, the PIKCA3 gene, and cytokins like the thrombopoietin gene [38, 39, 40, 41]. Furthermore, overrepresentations on 3q27–28 are common cytogenetic findings in severe dysplasias/carcinoma in situ, which may be a key event occurring early during carcinogenesis [42, 43].…”

Comparative Analysis of Gene Expression for Convergent Evolution of Camera Eye Between Octopus and Human

“…Moreover, we found that five out of the 14 genes were certainly involved in the function of the camera eyes of humans and octopuses. For example, diacylglycerol kinase ␥, which is expressed in the rod outer segment of the retina, was found in humans and octopuses, but not in the invertebrates examined except octopus (Stohr et al 1999). For another example, dihydroxyacetonephosphate acyltransferase is the peroxisomal key enzyme of plasmalogen biosynthesis in eye-lens epithelial cells (Thai et al 1999).…”