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David J Harris

Publications and source records attributed to David J Harris.

8 recordsLinked to original sources
PubMed2007

Candidate loci for Zimmermann-Laband syndrome at 3p14.3.

A male with 46,XY,t(3;17)(p14.3;q24.3) presented with gingival hyperplasia, hypertrichosis, unusually large ears and marked hypertrophy of the nose, characteristic of the Zimmermann-Laband syndrome (ZLS). Other features include large facial bones and mandibles, large protruding upper lip, enlarged fingers and toes, strabismus, and enlarged phallus. Knowledge of a 46,XX,t(3;8)(p21.2;q24.3) reported previously in a mother and daughter with ZLS suggests that the 3p14.3-p21.2 region may contain a gene responsible for ZLS. We have reassessed the chromosome 3 breakpoint region of the t(3;8) and revised its breakpoint location to 3p14.3, based upon an updated human genome sequence assembly. Using fluorescence in situ hybridization (FISH) with BAC clones, we have also identified a breakpoint spanning clone at 3p14.3 in our t(3;17) patient, thereby narrowing the breakpoint to a region of approximately 200 kb. These data suggest that the gene responsible for ZLS is located in 3p14.3 and implicates four likely candidate genes in this region: CACNA2D3, encoding a voltage-dependent calcium channel, LRTM1, a gene of unknown function embedded within CACNA2D3, WNT5A, encoding a secreted signaling protein of the WNT family, and ERC2, which codes for a synapse protein.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Synthesis, transport and accumulation of quinolizidine alkaloids in Lupinus albus L. and L. angustifolius L.

Each of the principal quinolizidine alkaloids (QA) found in both xylem and phloem exudates together with extracts from all component organs collected from bitter (cv. Lupini) and sweet (cv. Ultra) cultivars of Lupinus albus L. were quantified by gas chromatographic analyses throughout reproductive development. In addition to establishing the major translocated QA species estimates for fluxes of QA to developing fruits based on their sap composition and water economy showed that around half of the QA that accumulated in fruit tissues was due to synthesis in situ and half to translocation principally by phloem. Detailed analyses of QA in transport fluids and component organs were extended to reciprocal homo- and hetero-grafts using bitter (cv. Fest) and sweet (cv. Danja) cultivars of L. angustifolius L. These data confirmed that the majority of QA were synthesized in shoot tissues. In both lupin species feeding and analysis of deuterated QA (lupanine and 13-hydroxylupanine) were used as tracers to demonstrate direct redistribution of alkaloids by translocation from mature leaves in phloem.

Alkaloids↗
PubMed2005

Trisomy 8 mosaicism in a patient with heterotaxia.

Constitutional trisomy 8 mosaicism (CT8M) is a relatively rare trisomy in humans with a characteristic phenotype. We report an infant with the characteristic CT8M phenotype in addition to heterotaxia. A number of chromosomal abnormalities have been reported in association with laterality defects but this is the first time heterotaxia is reported in CT8M. In addition to expanding CT8M phenotype, our report may provide insight into the mechanism of heterotaxia.

Chromosomes, Human, Pair 8↗
PubMed2005

How much data are needed to resolve a difficult phylogeny?: case study in Lamiales.

Reconstructing phylogeny is a crucial target of contemporary biology, now commonly approached through computerized analysis of genetic sequence data. In angiosperms, despite recent progress at the ordinal level, many relationships between families remain unclear. Here we take a case study from Lamiales, an angiosperm order in which interfamilial relationships have so far proved particularly problematic. We examine the effect of changing one factor-the quantity of sequence data analyzed-on phylogeny reconstruction in this group. We use simulation to estimate a priori the sequence data that would be needed to resolve an accurate, supported phylogeny of Lamiales. We investigate the effect of increasing the length of sequence data analyzed, the rate of substitution in the sequences used, and of combining gene partitions. This method could be a valuable technique for planning systematic investigations in other problematic groups. Our results suggest that increasing sequence length is a better way to improve support, resolution, and accuracy than employing sequences with a faster substitution rate. Indeed, the latter may in some cases have detrimental effects on phylogeny reconstruction. Further molecular sequencing-of at least 10,000 bp-should result in a fully resolved and supported phylogeny of Lamiales, but at present the problematic aspects of this tree model remain.

Base Sequence↗
PubMed2004

Constitutional rearrangement of the architectural factor HMGA2: a novel human phenotype including overgrowth and lipomas.

Although somatic mutations in a number of genes have been associated with development of human tumors, such as lipomas, relatively few examples exist of germline mutations in these genes. Here we describe an 8-year-old boy who has a de novo pericentric inversion of chromosome 12, with breakpoints at p11.22 and q14.3, and a phenotype including extreme somatic overgrowth, advanced endochondral bone and dental ages, a cerebellar tumor, and multiple lipomas. His chromosomal inversion was found to truncate HMGA2, a gene that encodes an architectural factor involved in the etiology of many benign mesenchymal tumors and that maps to the 12q14.3 breakpoint. Similar truncations of murine Hmga2 in transgenic mice result in somatic overgrowth and, in particular, increased abundance of fat and lipomas, features strikingly similar to those observed in the child. This represents the first report of a constitutional rearrangement affecting HMGA2 and demonstrates the role of this gene in human growth and development. Systematic genetic analysis and clinical studies of this child may offer unique insights into the role of HMGA2 in adipogenesis, osteogenesis, and general growth control.

Abnormalities, Multiple↗
PubMed2003

Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA(Arg303X/Cys338Tyr).

Aldolase (E.C. 4.1.2.13), a homotetrameric protein encoded by the ALDOA gene, converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. Three isozymes are encoded by distinct genes. The sole aldolase present in red blood cells and skeletal muscle is the A isozyme. We report here the case of a girl of Sicilian descent with aldolase A deficiency. Clinical manifestations included transfusion-dependent anemia until splenectomy at age 3 and increasing muscle weakness, with death at age 4 associated with rhabdomyolysis and hyperkalemia. Sequence analysis of the ALDOA coding regions revealed 2 novel heterozygous ALDOA mutations in conserved regions of the protein. The paternal allele encoded a nonsense mutation, Arg303X, in the enzyme-active site. The maternal allele encoded a missense mutation, Cys338Tyr, predicted to cause enzyme instability. This is the most severely affected patient reported to date and only the second with both rhabdomyolysis and hemolysis.

Amino Acid Sequence↗