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At least 1,621 records · Page 90Linked to original sources
PubMed2002

The origin of conditional logic: does a cheater detection module exist?

The domain-specific hypothesis of L. Cosmides (1989) and L. Cosmides and J. Tooby (1989, 1992) positing that conditional logic has its origin in the evolution of social exchange and in the detection of potential cheaters was tested against a more domain-general hypothesis positing that adult reasoning is logical and that errors in conditional reasoning arise from misunderstandings, not from a lack of logicality. The results of 5 experiments with undergraduate students (n = 682 for Experiments 1-4; n = 188 for Experiment 5), which involved a series of selection tasks that yielded specific predictions about participant performance, were not consistent with the cheater detection hypothesis. Findings supported the misunderstandings hypothesis and imply that adults possess general-purpose logical competence versus domain-specific modules.

Adult↗
PubMed1986

Identification of Rhizobium plasmid sequences involved in recognition of Psophocarpus, Vigna, and other legumes.

Symbiotic DNA sequences involved in nodulation by Rhizobium must include genes responsible for recognizing homologous hosts. We sought these genes by mobilizing the symbiotic plasmid of a broad host-range Rhizobium MPIK3030 (= NGR234) that can nodulate Glycine max, Psophocarpus tetragonolobus, Vigna unguiculata, etc., into two Nod- Rhizobium mutants as well as into Agrobacterium tumefaciens. Subsequently, cosmid clones of pMPIK3030a were mobilized into Nod+ Rhizobium that cannot nodulate the chosen hosts. Nodule development was monitored by examining the ultrastructure of nodules formed by the transconjugants. pMPIK3030a could complement Nod- and Nif- deletions in R. leguminosarum and R. meliloti as well as enable A. tumefaciens to nodulate. Three non-overlapping sets of cosmids were found that conferred upon a slow-growing Rhizobium species, as well as on R. loti and R. meliloti, the ability to nodulate Psophocarpus and Vigna, thus pointing to the existence of three sets of host-specificity genes. Recipients harboring these hsn regions had truly broadened host-range since they could nodulate both their original hosts as well as MPIK3030 hosts.

Base Sequence↗
PubMed2002

Frequent chromosome aberrations revealed by molecular cytogenetic studies in patients with aniridia.

Seventy-seven patients with aniridia, referred for cytogenetic analysis predominantly to assess Wilms tumor risk, were studied by fluorescence in situ hybridization (FISH), through use of a panel of cosmids encompassing the aniridia-associated PAX6 gene, the Wilms tumor predisposition gene WT1, and flanking markers, in distal chromosome 11p13. Thirty patients were found to be chromosomally abnormal. Cytogenetically visible interstitial deletions involving 11p13 were found in 13 patients, 11 of which included WT1. A further 13 patients had cryptic deletions detectable only by FISH, 3 of which included WT1. Six of these, with deletions <500 kb, share a similar proximal breakpoint within a cosmid containing the last 10 exons of PAX6 and part of the neighboring gene, ELP4. Two of these six patients were mosaic for the deletion. The remaining four had chromosomal rearrangements: an unbalanced translocation, t(11;13), with a deletion including the WAGR (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) region, and three balanced rearrangements with what appear to be position effect breakpoints 3' of PAX6: (a) a t(7;11) with the 11p13 breakpoint approximately 30 kb downstream of PAX6, (b) a dir ins(12;11) with a breakpoint >50 kb from PAX6, and (c) an inv(11)(p13q13) with a breakpoint >75 kb downstream of PAX6. The proportion and spectrum of chromosome anomalies in familial (4/14, or 28.5%) and sporadic (26/63, or 41%) cases are not significantly different. An unexpectedly high frequency of chromosomal rearrangements is associated with both sporadic and familial aniridia in this cohort.

Aniridia↗
PubMed2003

Mapping the Wolf-Hirschhorn syndrome phenotype outside the currently accepted WHS critical region and defining a new critical region, WHSCR-2.

In an attempt to define the distinctive Wolf-Hirschhorn syndrome (WHS) phenotype, and to map its specific clinical manifestations, a total of eight patients carrying a 4p16.3 microdeletion were analyzed for their clinical phenotype and their respective genotypes. The extent of each individual deletion was established by fluorescence in situ hybridization, with a cosmid contig spanning the genomic region from MSX1 (distal half of 4p16.1) to the subtelomeric locus D4S3359. The deletions were 1.9-3.5 Mb, and all were terminal. All the patients presented with a mild phenotype, in which major malformations were usually absent. It is worth noting that head circumference was normal for height in two patients (those with the smallest deletions [1.9 and 2.2 Mb]). The currently accepted WHS critical region (WHSCR) was fully preserved in the patient with the 1.9-Mb deletion, in spite of a typical WHS phenotype. The deletion in this patient spanned the chromosome region from D4S3327 (190 b4 cosmid clone included) to the telomere. From a clinical point of view, the distinctive WHS phenotype is defined by the presence of typical facial appearance, mental retardation, growth delay, congenital hypotonia, and seizures. These signs represent the minimal diagnostic criteria for WHS. This basic phenotype maps distal to the currently accepted WHSCR. Here, we propose a new critical region for WHS, and we refer to this region as "WHSCR-2." It falls within a 300-600-kb interval in 4p16.3, between the loci D4S3327 and D4S98-D4S168. Among the candidate genes already described for WHS, LETM1 (leucine zipper/EF-hand-containing transmembrane) is likely to be pathogenetically involved in seizures. On the basis of genotype-phenotype correlation analysis, dividing the WHS phenotype into two distinct clinical entities, a "classical" and a "mild" form, is recommended for the purpose of proper genetic counseling.

Abnormalities, Multiple↗
PubMed1987

The human growth hormone gene locus: structure, evolution, and allelic variations.

Genomic clones containing the closely related genes for human growth hormone (hGH) and chorionic somatomammotropin (hCS) were obtained from genomic bacteriophage lambda and cosmid libraries. The entire GH/CS chromosomal locus was reconstructed utilizing overlapping restriction fragments characterized from the isolated clones. The hGH/hCS locus contains two GH genes and three CS genes spanning 48 kb of DNA in the order: 5'-(hGH-1/hCS-5/hCS-1/hGH-2/hCS-2)-3', confirming analysis of cosmid clones obtained from a different human library (Barsh et al., 1983). To complete the characterization of the hCS genes, the nucleotide sequence of the hCS-5 gene was determined. Sequence analysis revealed a mutation of the 5' splice site at the exon II-intron B boundary, suggesting that the hCS-5 gene is a pseudogene. The nucleotide sequence of an allelic variant of the hCS-2 gene was determined and found to contain a single amino acid substitution and the deletion of a single codon. The hGH/hCS gene locus was further characterized by the localization of at least 27 Alu-type repetitive sequences and identification of three unique sequences in the vicinity of several hGH and hCS genes which define the probable breakpoints of the evolutionary duplication units. These data, combined with the nucleotide sequences of all five GH and CS genes, indicate that the hGH/hCS gene locus has evolved by duplication mechanisms. Evidence for the occurrence of at least one gene conversion event involving the hCS-1 gene precursor and the hCS-2 gene was found, indicating that the hGH/hCS gene locus has evolved by concerted mechanisms. The structure of the hCS genes is discussed in light of recent studies of CS genes from other mammalian species.

Alleles↗
PubMed1991

Homologous and unique G protein alpha subunits in the nematode Caenorhabditis elegans.

A cDNA corresponding to a known G protein alpha subunit, the alpha subunit of Go (Go alpha), was isolated and sequenced. The predicted amino acid sequence of C. elegans Go alpha is 80-87% identical to other Go alpha sequences. An mRNA that hybridizes to the C. elegans Go alpha cDNA can be detected on Northern blots. A C. elegans protein that crossreacts with antibovine Go alpha antibody can be detected on immunoblots. A cosmid clone containing the C. elegans Go alpha gene (goa-1) was isolated and mapped to chromosome I. The genomic fragments of three other C. elegans G protein alpha subunit genes (gpa-1, gpa-2, and gpa-3) have been isolated using the polymerase chain reaction. The corresponding cosmid clones were isolated and mapped to disperse locations on chromosome V. The sequences of two of the genes, gpa-1 and gpa-3, were determined. The predicted amino acid sequences of gpa-1 and gpa-3 are only 48% identical to each other. Therefore, they are likely to have distinct functions. In addition they are not homologous enough to G protein alpha subunits in other organisms to be classified. Thus C. elegans has G proteins that are identifiable homologues of mammalian G proteins as well as G proteins that appear to be unique to C. elegans. Study of identifiable G proteins in C. elegans may result in a further understanding of their function in other organisms, whereas study of the novel G proteins may provide an understanding of unique aspects of nematode physiology.

Amino Acid Sequence↗
PubMed1995

Non-random deletions at the dihydrofolate reductase locus of Chinese hamster ovary cells induced by alpha-particles simulating radon.

This study presents the physical characterization of mutants induced in mammalian cells by high linear energy transfer alpha-particle radiation that simulates exposure to radon daughters. Alpha-Particles from accelerated 4He at 150 keV/microns were used to induce 20 Chinese hamster ovary mutants that are deficient in dihydrofolate reductase (DHFR) activity. Parental cells were the hemizygous UA21 line. Cell survival decreased exponentially in response to radiation dose from 0.25 to 1.75 Gy. Mutants were obtained at 1.0 (17/20) and 1.25 Gy (3/20); treatments at 1.50 Gy failed to yield mutants. The induced frequency of mutation was 2.3 x 10(-6) at the 1.0 Gy dose, approximately 18-fold greater than the spontaneous mutation rate at this locus. DNA of the 20 confirmed null mutants were examined for alterations in the 25 kb DHFR gene by Southern blotting using a mixed probe that scans a continuous 34 kb of sequence. Deletions were the most prevalent induced change (18/20). Of the two point mutants, DNA sequencing showed that one carries a T:A-->G:C base substitution that changed Val135 to Gly in exon 5; carcinogen-induced reversion to a DHFR+ phenotype at a frequency of 3 x 10(-6) confirmed that the other also carried a single base change. The distribution of deletion break sites in the DHFR locus was non-random. In half of the mutants deletion break sites were clustered within a single 9.4 kb DHFR intron. Fine mapping within the gene of 14 mutants by Southern blotting localized 10 distinct break sites to small restriction fragments (< 2 kb). Results of this mapping indicated that three unequivocally independent mutants apparently arose by the same deletion and that others shared single break sites. Deletion sizes in these mutants were determined by Southern analysis using six cosmids and two plasmid probes that together span approximately 500 kb of sequence in the region of the DHFR locus. Probing blots with the cosmids defined a maximal deletion size in 15/17 mutants and confirmed that deletions extended < 150 kb in 11, a qualitatively different result from that previously obtained after a similar analysis of gamma-ray-induced DHFR- mutants. Since deletions were non-randomly distributed, typically less than replicon size and spared regions containing matrix attachment sites, the results suggest a model whereby alpha-particles induce double-strand breaks in accessible chromatin loops.

Alpha Particles↗
PubMed1993

Molecular cloning and duplication of the nematode sex-determining gene tra-1.

The autosomal sex-determining gene tra-1 plays a major role in controlling sexual phenotype in the nematode Caenorhabditis elegans. This gene is the terminal global regulator in a well-characterized cascade of sex-determining genes. It governs all aspects of somatic sexual differentiation, and it also has important functions in governing germ-line differentiation. Previous genetic analyses have led to the characterization of many loss-of-function (masculinizing) and gain-of-function (dominant feminizing) alleles, and to models for the functions and regulation of tra-1. The gene was cloned by identifying linked transposon insertions, about 200 kb away from tra-1. From this starting point a series of YAC, cosmid and phage clones were assembled into a genomic walk covering over 400 kb. Much of this region was found to be unrepresented in the cosmid database that covers most of the C. elegans genome. This deficit is largely or wholly due to the presence of sequences that cannot be cloned in rec+bacterial hosts. The ratio of physical map distances to recombinational map distances in the tra-1 region of the genome appears to be unusually low, indicating considerable local map expansion. The location of tra-1 within the cloned region was determined using a variety of tra-1 mutations that are associated with physical rearrangements of the gene. One of these is a 14-kb deletion, which behaves as a null allele. Another rearrangement, eDp24, is a tandem duplication of 22kb. Genetic analysis demonstrates that eDp24 carries two incomplete copies of tra-1, and that these copies appear to interact, suggesting some form of negative autoregulation at this locus. Three variant forms of the tra-1 locus have been identified in different natural isolates of C. elegans.

Alleles↗
PubMed1993

Mutation in the bimD gene of Aspergillus nidulans confers a conditional mitotic block and sensitivity to DNA damaging agents.

Mutation in the bimD gene of Aspergillus nidulans results in a mitotic block in anaphase characterized by a defective mitosis. Mutation in bimD also confers, at temperatures permissive for the mitotic arrest phenotype, an increased sensitivity to DNA damaging agents, including methyl methanesulfonate and ultraviolet light. In order to better understand the relationship between DNA damage and mitotic progression, we cloned the bimD gene from Aspergillus. A cosmid containing the bimD gene was identified among pools of cosmids by cotransformation with the nutritional selective pyrG gene of a strain carrying the recessive, temperature-sensitive lethal bimD6 mutation. The bimD gene encodes a predicted polypeptide of 166,000 daltons in mass and contains amino acid sequence motifs similar to those found in some DNA-binding transcription factors. These sequences include a basic domain followed by a leucine zipper, which together are called a bZIP motif, and a carboxyl-terminal domain enriched in acidic amino acids. Overexpression of the wild-type bimD protein resulted in an arrest of the nuclear division cycle that was reversible and determined to be in either the G1 or S phase of the cell cycle. Our data suggest that bimD may play an essential regulatory role relating to DNA metabolism which is required for a successful mitosis.

Amino Acid Sequence↗
PubMed1996

A genetic linkage map of the male goat genome.

This paper presents a first genetic linkage map of the goat genome. Primers derived from the flanking sequences of 612 bovine, ovine and goat microsatellite markers were gathered and tested for amplification with goat DNA under standardized PCR conditions. This screen made it possible to choose a set of 55 polymorphic markers that can be used in the three species and to define a panel of 223 microsatellites suitable for the goat. Twelve half-sib paternal goat families were then used to build a linkage map of the goat genome. The linkage analysis made it possible to construct a meiotic map covering 2300 cM, i.e., > 80% of the total estimated length of the goat genome. Moreover, eight cosmids containing microsatellites were mapped by fluorescence in situ hybridization in goat and sheep. Together with 11 microsatellite-containing cosmids previously mapped in cattle (and supposing conservation of the banding pattern between this species and the goat) and data from the sheep map, these results made the orientation of 15 linkage groups possible. Furthermore, 12 coding sequences were mapped either genetically or physically, providing useful data for comparative mapping.

Animals↗
PubMed1997

P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: correlation of physical and cytogenetic maps in chromosomal region 86E-87F.

We have established a collection of 2460 lethal or semi-lethal mutant lines using a procedure thought to insert single P elements into vital genes on the third chromosome of Drosophila melanogaster. More than 1200 randomly selected lines were examined by in situ hybridization and 90% found to contain single insertions at sites that mark 89% of all lettered subdivisions of the Bridges' map. A set of chromosomal deficiencies that collectively uncover approximately 25% of the euchromatin of chromosome 3 reveal lethal mutations in 468 lines corresponding to 145 complementation groups. We undertook a detailed analysis of the cytogenetic interval 86E-87F and identified 87 P-element-induced mutations falling into 38 complementation groups, 16 of which correspond to previously known genes. Twenty-one of these 38 complementation groups have at least one allele that has a P-element insertion at a position consistent with the cytogenetics of the locus. We have rescued P elements and flanking chromosomal sequences from the 86E-87F region in 35 lines with either lethal or genetically silent P insertions, and used these as probes to identify cosmids and P1 clones from the Drosophila genome projects. This has tied together the physical and genetic maps and has linked 44 previously identified cosmid contigs into seven "super-contigs" that span the interval. STS data for sequences flanking one side of the P-element insertions in 49 lines has identified insertions in the alphagamma element at 87C, two known transposable elements, and the open reading frames of seven putative single copy genes. These correspond to five known genes in this interval, and two genes identified by the homology of their predicted products to known proteins from other organisms.

Alleles↗
PubMed1998

Chromosome walking to the AVR1-CO39 avirulence gene of Magnaporthe grisea: discrepancy between the physical and genetic maps.

The avrCO39 gene conferring avirulence toward rice cultivar CO39 was previously mapped to chromosome 1 of Magnaporthe grisea between cosegregating markers CH5-120H and 1.2H and marker 5-10-F. In the present study, this region of the chromosome was physically mapped using RecA-mediated Achilles' cleavage. Cleavage of genomic DNA sequences within CH5-120H and 5-10-F liberated a 610-kb restriction fragment, representing the physical distance between these markers. Chromosome walking was initiated from both markers but was curtailed due to the presence of repetitive DNA sequences and the absence of overlapping clones in cosmid libraries representing several genome equivalents. These obstacles were overcome by directly subcloning the target region after release by Achilles' cleavage and a contig spanning avrCO39 was thus assembled. Transformation of two cosmids into a virulent recipient strain conferred a cultivar-specific avirulence phenotype thus confirming the cloning of avrCO39. Meiotic crossover points were unevenly distributed across this chromosomal region and were clustered around the avrCO39 locus. A 14-fold variation in the relationship between genetic and physical distance was measured over the avrCO39 chromosomal region. Thus the poor correlation of physical to genetic distance previously observed in M. grisea appears to be manifested over relatively short distances.

Chromosome Mapping↗
PubMed1992

Identification of genes using oligonucleotides corresponding to splice site consensus sequences.

The identification of genes in genomic DNA presents challenging technical difficulties. We show here the feasibility of using short oligonucleotides based on the consensus sequences surrounding intron-exon junctions to detect random phage and cosmid clones containing genes both through the analysis of DNA blots and by direct screening. Three degenerate oligonucleotides, a 10-mer corresponding to the 5' splice junction and a 9-mer and a 15-mer corresponding to the 3' splice junction, were tested on the known intron-exon boundaries of the cloned human proteolipid protein (PLP) gene at hybridization and washing temperatures appropriate to their length and composition. All predicted hybridizations were observed. The oligonucleotides were also used to identify random genomic plasmid and cosmid clones containing putative intron-exon junctions; the presence of genes in these clones was supported by RNA blot analysis and by cross-hybridization to DNA from other species. This technique should facilitate the identification of genes for inherited diseases by positional cloning studies and will assist in the identification of genes in random clones for the human genome project.

Base Sequence↗
PubMed1992

Characterization of a 1.0 Mb YAC contig spanning two chromosome breakpoints related to Menkes disease.

Menkes disease, an X-linked recessive disorder of copper metabolism, has recently been mapped to Xq13.3 by two Menkes patients carrying chromosome rearrangements within this region. The breakpoints have been investigated by nonisotopic in situ suppression hybridization using YACs isolated from this region with the flanking markers DXS56 and PGK1. Three YACs were extending over the breakpoints at Xq13.3 and were shown to be overlapping by partial digest restriction maps, IRS-PCR fingerprinting and by the presence of common cosmid clones. These cosmids were subcloned and one of the single copy probes detected both breakpoints using rare-cutting restriction enzyme digests of the patients. All the results together localize the breakpoints to about 100 kb within the overlapping region of the YACs. Mapping of both breakpoints in a 1 Mb YAC contig implies that these YACs contain at least partially, the gene responsible for Menkes disease.

Chromosome Aberrations↗
PubMed1993

A gene from chromosome 4p16.3 with similarity to a superfamily of transporter proteins.

We have previously used exon amplification to identify the ADD1 gene in cosmid Y24 from the Huntington's disease (HD) region of 4p16.3. The same technique has now yielded a second gene from this cosmid. This gene appears to encode a novel member of a superfamily of transporter proteins that includes active and passive transporters in a number of species. The predicted protein of 455 amino acids displays sequence similarity with the E. coli tetracycline resistance efflux protein encoded by cloning vector pBR322, and with a number of related transporters. This gene should open a route to isolating additional mammalian members of this growing superfamily.

Amino Acid Sequence↗
PubMed1994

A heat shock gene at 14q22: mapping and expression.

Heat shock proteins (HSP) belong to a family of highly homologous proteins that are encoded by several genes and function as protein chaperones. A number of HSP genes have been described in the major histocompatibility complex (MHC) on chromosome 6. We have cloned and mapped one chromosome 14 HSP gene (HSPA2) using a genomic probe (pH2.3) derived from one of the HSP genes present in the MHC, which was previously shown to also detect sequences on chromosome 14. Screening of a chromosome 14-specific cosmid library yielded one relevant clone that contains an HSP-like sequence, showing a high degree of identity with the HSP genes from the MHC and with HSP70.2 (Hspa2) in the mouse. This new HSP gene is expressed abundantly in muscle, heart, oesophagus and brain, and to a lesser extent in testis. Its localization to 14q22 was established by using a somatic cell hybrid panel and FISH analysis. A pentanucleotide repeat motif, showing seven alleles, was also identified in the cosmid clone.

Amino Acid Sequence↗
PubMed1994

A YAC clone map spanning 7.5 megabases of human chromosome band Xq28.

Xq28 has been of special interest in human genetics because a large number of diseases map to this region. As a step in the molecular analysis of the as yet uncloned disease genes, and as a test for the detailed analysis of larger regions of the genome, we have constructed YAC clone contigs covering the 7.5 Mb region between IDS to the telomere on the long arm of the human X chromosome. Contigs were assembled and verified by an integrated hybridization-based strategy. Data was combined from the physical map, from YAC and cosmid mapping experiments, and from the localization of specific transcripts in the region. Two gaps in the YAC map of 250 and 100 kb were covered in part by the aid of cosmid clones, but small gaps of 50 kb each remain. The cloned region is expected to contain yet unidentified genes for at least ten genetic diseases. The construction of ordered YAC clone contigs of Xq28 represents an important step in the molecular identification of these genes, and the further analysis of one of the genetically most interesting regions of the human genome.

Chromosomes, Artificial, Yeast↗
PubMed1994

X-linked mixed deafness (DFN3): cloning and characterization of the critical region allows the identification of novel microdeletions.

We have found that the microsatellite marker AFM207zg5 (DXS995) maps to all previously described deletions which are associated with X-linked mixed deafness (DFN3) with or without choroideremia and mental retardation. Employing this marker and pHU16 (DXS26) we have identified two partially overlapping yeast artificial chromosome clones which were used to construct a complete 850 kb cosmid contig. Cosmids from this contig have been tested by Southern blot analysis on DNA from 16 unrelated males with X-linked deafness. Two novel microdeletions were detected in patients which exhibit the characteristic DFN3 phenotype. Both deletions are completely contained within one of the known DFN3-deletions, but one of them does not overlap with two previously described deletions in patients with contiguous gene syndromes consisting of DFN3, choroideremia, and mental retardation. Assuming that only a single gene is involved, this suggests that the DFN3 gene spans a chromosomal region of at least 400 kb.

Chromosome Walking↗