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K M Weiss

Publications and source records attributed to K M Weiss.

At least 37 records · Page 2Linked to original sources

Relationship between the genomic organization and the overlapping embryonic expression patterns of the zebrafish dlx genes.

To understand the relationship between the expression and the genomic organization of the zebrafish dlx genes, we have determined the genomic structure of the dlx2 and dlx4 loci. This led to the identification of the zebrafish dlx1 and dlx6 genes, which are closely linked to dlx2 and dlx4, respectively. Therefore, the inverted convergent configuration of Dlx genes is conserved among vertebrates. Analysis of the expression patterns of dlx1 and dlx6 showed striking similarities to those of dlx2 and dlx4, respectively, the genes to which they are linked. Furthermore, the expression patterns of dlx3 and dlx7, which likely constitute a third pair of convergently transcribed genes, are indistinguishable. Thus, the overlapping expression patterns of linked Dlx genes during embryonic development suggest that they share cis-acting sequences that control their spatiotemporal expression. The evolutionary conservation of the genomic organization and combinatorial expression of Dlx genes in distantly related vertebrates suggest tight control mechanisms that are essential for their function during development.

Amino Acid Sequence↗

Patterning of the mammalian dentition in development and evolution.

The mammalian dentition is a segmented organ system with shape differences among its serially homologous elements (individual teeth). It is believed to have evolved from simpler precursors with greater similarities in shape among teeth, and a wealth of descriptive data exist on changes to the dentition that have occurred within mammals. Recent progress has been made in determining the genetic basis of the processes that form an individual tooth, but patterning of the dentition as a whole (i.e. the number, location and shape of the teeth) is less well understood. In contrast to similarly organized systems, such as the vertebral column and limb, Hox genes are not involved in specifying differences among elements. Nevertheless, recent work on a variety of systems is providing clues to the transcription factors and extracellular signalling molecules involved.

Animals↗

Genomic analysis of a new mammalian distal-less gene: Dlx7.

We have cloned a new Dlx gene (Dlx7) from human and mouse that may represent the mammalian orthologue of the newt gene NvHBox-5. The homeodomains of these genes are highly similar to all other vertebrate Dlx genes, and regions of similarity also exist between mammalian Dlx7 and a subset of vertebrate Dlx genes downstream of the homeodomain. The sequence divergence between human and mouse Dlx7 in these regions is greater than that predicted from comparisons of other vertebrate Dlx genes, however, and there is little sequence similarity upstream of the homeodomain both between these two genes and with other Dlx genes. We present evidence for alternative splicing of mouse Dlx7 upstream of the homeodomain that may account for some of this divergence. We have mapped human DLX7 distal to the 5' end of the HOXB cluster at an estimated distance of between 1 and 2 Mb by FISH. Both the human and the mouse Dlx7 are shown to be closely linked to Dlx3 in a convergently transcribed orientation. These mapping results support the possibility that vertebrate distal-less genes have been duplicated in concert with the Hox clusters.

Amino Acid Sequence↗

Numerous members of the Sox family of HMG box-containing genes are expressed in developing mouse teeth.

We used RT-PCR to detect the expression in mouse molar and incisor tooth germs of 14 of the 19 known members of the Sox family of HMG box-containing transcription factors. These sequences fell into all 6 of the main subdivisions of the Sox family. In general, the relative transcript abundance of the different Sox genes is similar between molar and incisor tooth germs, although 3 low-abundance transcripts were found in only a single tooth type. The expression of Sox genes during tooth development has not been reported previously and further experiments will be required to determine their role in this process.

Animals↗

The evolution of the vertebrate Dlx gene family.

The vertebrate Dlx gene family consists of homeobox-containing transcription factors distributed in pairs on the same chromosomes as the Hox genes. To investigate the evolutionary history of Dlx genes, we have cloned five new zebrafish family members and have provided additional sequence information for two mouse genes. Phylogenetic analyses of Dlx gene sequences considered in the context of their chromosomal arrangements suggest that an initial tandem duplication produced a linked pair of Dlx genes after the divergence of chordates and arthropods but prior to the divergence of tunicates and vertebrates. This pair of Dlx genes was then duplicated in the chromosomal events that led to the four clusters of Hox genes characteristic of bony fish and tetrapods. It is possible that a pair of Dlx genes linked to the Hoxc cluster has been lost from mammals. We were unable to distinguish between independent duplication and retention of the ancestral state of bony vertebrates to explain the presence of a greater number of Dlx genes in zebrafish than mammals. Determination of the linkage relationship of these additional zebrafish Dlx genes to Hox clusters should help resolve this issue.

Animals↗

A simple clinical assessment of attention in schizophrenia.

Although attentional dysfunction is considered a predominant feature of schizophrenia, it is seldom quantitatively assessed in clinical practice. A simple paper-and-pencil test of selective attention (Ruff et al., 1986) provides a 5-min assessment with theoretical relevance for schizophrenia. Thirty schizophrenic subjects performed the 2 and 7 Selective Attention Test, which measures speed and accuracy, and compares controlled and automatic information processing. Ninety percent of the subjects displayed automatic processing. Speed was severely impaired, and accuracy was less so. Sixty-seven percent of the schizophrenic subjects performed in the normal range (+/-1 SD) for accuracy, but only 23% scored in the normal range for speed. Speed and accuracy were moderately correlated. Although theories of a lateralized deficit were not supported, the results are consistent with a hypothesized frontal lobe dysfunction. The automatic processing demonstrated may represent old learning. Poor controlled processing may preclude the acquisition of automatic functioning. This selective attention test may provide a measure of severity of cognitive impairment relevant to daily life functioning.

Adult↗

Is there a paradigm shift in genetics? Lessons from the study of human diseases.

The flood of genetic data made possible by recent technological advances has led to a number of important changes in our conceptual model, or working "paradigm," of genetics. Among these changes are recognition that (1) most mutations are unique; (2) there are many alleles at every locus, not just two; (3) these alleles have a hierarchical, or cladistic, history-dependent structure and geographic distribution; (3) the genotype-to-phenotype relationship is complex and quantitative, even for single-locus traits; (4) genotype-phenotype relationships often depend on the organization of the genome into linkage groups, gene families, and the like; and (5) genes affecting quantitative traits can be individually identified rather than solely being viewed as a polygenic aggregate, and these genes each have the same characteristics as genes for single-locus phenotypes. The latter provides a profound unifying impact on biology by reconciling long-standing conceptual differences on qualitative vis-a-vis quantitative phenotypes and their relative importance and evolution. Many of the data that have led to these advances have been generated in the study of genes associated with diseases in human populations. The conceptual changes affect all of biology, but are especially important in the human context, because the amount, complexity, and historical dependence of the variation in the human genome have serious societal implications regarding the epistemology of genetic causation and applications in public health. But whether these changes constitute a real "paradigm shift" in genetics, or are merely adjustments in the classical models developed early in this century, is unclear.

Alleles↗

Dlx and other homeobox genes in the morphological development of the dentition.

The dentition is a segmental system whose evolution and morphology bears analogy to the evolution of segmentation in the vertebral column and limb. Combinatorial expression of members of the large "Hox" class of homeobox regulatory genes has been shown to play an important role in positional specification in these skeletal systems. This raises the possibility that homeobox genes are also used for positional specification in the dentition, and several homeobox genes are known to be expressed in developing teeth. To identify additional dentally expressed homeobox genes, cDNA from from murine tooth germs at 9.5, 14.5, and 17.5 days gestational age was amplified by PCR using sets of degenerate primers to the homeodomains of 18 different classes of homeobox genes. Amplification products were cloned and sequenced and compared to known gene sequences. To date this approach has confirmed the presence of Msx1, Msx2, Dlx1, and Dlx2, and identified several other homeobox genes not previously known to be expressed in teeth: Dbx, MHox, and Mox2A, plus an a additional Dlx gene, Dlx7. The Msx and Dlx genes are the best current candidates for a combinatorial mechanism that controls the differentiation of structures within and between teeth, and perhaps also the evolution of those structures.

Amino Acid Sequence↗

Distal-less and other homeobox genes in the development of the dentition.

The mammalian tooth develops through an interaction between two tissue layers of different embryologic origin. A number of transcription factors and as well as two members of the Msx class of homeobox genes have been shown to be involved in the histogenesis of the mammalian tooth. This raised the possibility that other homeobox genes might be involved in dental morphogenesis. We have amplified mouse tooth germ cDNA from three different gestational ages by the polymerase chain reaction with degenerate primers for 18 classes of homeobox genes. Members of several classes have been isolated, including the Msx genes, two Dlx genes, and the Dbx, MHox, Mox2A genes. One of the Dlx genes, Dlx-7, had not previously been reported in mammals, and some details are presented of its cDNA sequence. This work plus that of other investigators has shown that at least six Dlx genes are expressed in developing teeth or in first branchial arches, suggesting the possibility that these genes are involved in specifying complexity within or between teeth. The screening approach with degenerate primers is a successful way to identify new as well as previously known regulatory genes expressed in developing tooth embryos.

Amino Acid Sequence↗

American origins.

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Americas↗

Proportional hazards analysis of diarrhea due to enterotoxigenic Escherichia coli and breast feeding in a cohort of urban Mexican children.

Ninety-eight women-infant pairs were followed for up to 50 weeks in the northern part of Guadalajara, Mexico, from August 1986 to July 1987 as part of a community-based, prospective study of the relation between infant feeding patterns and enterotoxigenic Escherichia coli producing heat-labile toxin (LT-ETEC) diarrheal disease. Strictly formula-fed children had an incidence of diarrhea over three times that of strictly breast-fed infants and twice that of breast-fed and supplementally fed children. Strictly formula-fed infants colonized by LT-ETEC were symptomatic for diarrhea nearly three times as often as strictly breast-fed infants and twice as often as infants receiving a mixed diet. The fitting of parametric hazard models to durations until LT-ETEC colonization revealed that the hazard for the first colonization was time invariant. The hazard of diarrhea increased by 400-500% during the rainy season or among children 3 months of age or older who received avena, a barley drink. The best-fitting hazard models to durations until symptomatic expression of LT-ETEC infection all increased through time. This hazard was inversely impacted by the overall amount of LT-ETEC-specific, immunoglobulin A antibodies the infant received via the mother's breast milk and by the provision of traditional medicinal teas.

Bacterial Toxins↗

Plasma lipids and diet of the Mvskoke Indians.

Plasma lipids, lipoproteins, and apolipoproteins were measured in 123 female and 57 male Mvskoke Indians, a population of American Indians with a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). Dietary patterns were assessed with a food-frequency questionnaire. There were no differences in total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), apolipoproteins A-I or B in female Indians with and without diabetes. In males with diabetes, however, LDL-C was lower. Triglyceride and fasting plasma glucose were higher in subjects with diabetes. Total cholesterol and LDL-C were lower and HDL-C was higher than age and sex-matched Lipid Research Clinics values, especially for subjects with diabetes. This is surprising given that the diet of Mvskoke Indians contains foods high in total fat, saturated fatty acids, and cholesterol. We may explain, in part, the low incidence of coronary heart disease in this population.

Adult↗

Optimizing utilization of DNA from rare or archival anthropological samples.

There is widespread interest in obtaining genetic samples from human populations worldwide for various studies of human genetic diversity. Many samples exist today only in the form of small, rare, irreplaceable, or archival samples, such as material from ancient bone, hair bulbs, or remnants of samples collected in the field decades ago for the purpose of protein and blood type analysis. Here, we describe the application of an approach to amplify DNA, which we call adapter attachment and amplification (AAA). This approach is useful for amplifying the genome in a reasonably representative way from small amounts of starting material using standard PCR-based methods. We apply a version of these methods to DNA extracted from washed red blood cells collected in the 1960s and 1970s in the Amazon basin. AAA and similar approaches may make the analysis of archival samples possible without exhausting that irreplaceable material and may lead to greatly improved efficiency in collecting and using new anthropological genetic samples.

Anthropology↗