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C M Abbott

Publications and source records attributed to C M Abbott.

At least 19 recordsLinked to original sources
PubMed2003

A linkage map for the hybridising toads Bombina bombina and B. variegata (Anura: Discoglossidae).

Stable hybrid zones in which ecologically divergent taxa give rise to a range of recombinants are natural laboratories in which the genetic basis of adaptation and reproductive isolation can be unraveled. One such hybrid zone is formed by the fire-bellied toads Bombina bombina and B. variegata (Anura: Discoglossidae). Adaptations to permanent and ephemeral breeding habitats, respectively, have shaped numerous phenotypic differences between the taxa. All of these are, in principle, candidates for a genetic dissection via QTL mapping. We present here a linkage map of 28 codominant and 10 dominant markers in the Bombina genome. In an F2 cross, markers that were mainly microsatellites, SSCPs or allozymes were mapped to 20 linkage groups. Among the 40 isolated CA microsatellites, we noted a preponderance of compound and frequently interleaved CA-TA repeats as well as a striking polarity at the 5' end of the repeats.

Animals↗
PubMed2001

Comparative genomic analysis of genes encoding translation elongation factor 1B(alpha) in human and mouse shows EEF1B1 to be a recent retrotransposition event.

We have characterized genomic loci encoding translation elongation factor 1B(alpha) (eEF1B(alpha)) in mice and humans. Mice have a single structural locus (named Eef1b2) spanning six exons, which is ubiquitously expressed and maps close to Casp8 on mouse chromosome 1, and a processed pseudogene. Humans have a single intron-containing locus, EEF1B2, which maps to 2q33, and an intronless paralogue expressed only in brain and muscle (EEF1B3). Another locus described previously, EEF1B1, is actually a processed pseudogene on chromosome 15 corresponding to an alternative splice form of EEF1B2. Our study illustrates the value of comparative mapping in distinguishing between processed pseudogenes and intronless paralogues.

Alternative Splicing↗
PubMed2001

Of mice, men and motor neurons.

The use of mouse models has been of particular importance in studying the pathogenesis of amyotrophic lateral sclerosis. Here, we describe both transgenic and classical mutants for which the genetic lesion is known. We draw attention, wherever possible, to pathological factors common to multiple models.

Amyotrophic Lateral Sclerosis↗
PubMed2000

Two opposing effects of mismatch repair on CTG repeat instability in Escherichia coli.

The expansion of normally polymorphic CTG microsatellites in certain human genes has been identified as the causative mutation of a number of hereditary neurological disorders, including Huntington's disease and myotonic dystrophy. Here, we have investigated the effect of methyl-directed mismatch repair (MMR) on the stability of a (CTG)43 repeat in Escherichia coli over 140 generations and find two opposing effects. In contrast to orientation-dependent repeat instability in wild-type E. coli and yeast, we observed no orientation dependence in MMR- E. coli cells and suggest that, for the repeat that we have studied, orientation dependence in wild-type cells is mainly caused by functional mismatch repair genes. Our results imply that slipped structures are generated during replication, causing single triplet expansions and contractions in MMR- cells, because they are left unrepaired. On the other hand, we find that the repair of such slipped structures by the MMR system can go awry, resulting in large contractions. We show that these mutS-dependent contractions arise preferentially when the CTG sequence is encoded by the lagging strand. The nature of this orientation dependence argues that the small slipped structures that are recognized by the MMR system are formed primarily on the lagging strand of the replication fork. It also suggests that, in the presence of functional MMR, removal of 3 bp slipped structures causes the formation of larger contractions that are probably the result of secondary structure formation by the CTG sequence. We rationalize the opposing effects of MMR on repeat tract stability with a model that accounts for CTG repeat instability and loss of orientation dependence in MMR- cells. Our work resolves a contradiction between opposing claims in the literature of both stabilizing and destabilizing effects of MMR on CTG repeat instability in E. coli.

Adenosine Triphosphatases↗
PubMed1999

BRK/Sik expression in the gastrointestinal tract and in colon tumors.

Clones encoding the breast tumor kinase BRK were isolated from a normal human small intestinal cDNA library that was screened with the cDNA encoding the mouse epithelial-specific tyrosine kinase Sik. Although BRK and Sik share only 80% amino acid sequence identity, Southern blot hybridizations confirmed that the two proteins are orthologues. Sik was mapped to mouse distal chromosome 2, which shows conservation of synteny with human chromosome 20q13.3, the location of the BRK gene. BRK expression was examined in the normal gastrointestinal tract, colon tumor cell lines, and primary colon tumor samples. Like Sik, BRK is expressed in normal epithelial cells of the gastrointestinal tract that are undergoing terminal differentiation. BRK expression also increased during differentiation of the Caco-2 colon adenocarcinoma cell line. Modest increases in BRK expression were detected in primary colon tumors by RNase protection, in situ hybridization, and immunohistochemical assays. The BRK tyrosine kinase appears to play a role in signal transduction in the normal gastrointestinal tract, and its overexpression may be linked to the development of a variety of epithelial tumors.

Amino Acid Sequence↗
PubMed1998

Evaluation of Lama5 as a candidate for the mouse ragged (Ra) mutation.

The laminin alpha5 chain is a component of the basement membranes of many developing and adult tissues. The mouse laminin alpha5 chain gene (Lama5) has been mapped close to the locus of the semidominant ragged (Ra) mutation on distal chromosome 2. The cause of the Ra mutation, which is usually lethal in the homozygous state, has not been determined. We have investigated whether a defect in Lama5 is responsible for the ragged mutation, using the RaJ strain. No differences in the level of the laminin alpha5 chain transcript were found in placental RNA from homozygous RaJ mutant embryos compared to normal littermates. Antiserum raised against a recombinant laminin alpha5 chain polypeptide stained the basement membranes of both normal and homozygous mutant embryos to a similar extent. More precise mapping of Lama5 on an interspecific Ra backcross indicated that Lama5 is proximal to the Ra locus. These results exclude Lama5 as a candidate gene for the Ra mutation.

Animals↗
PubMed1998

The lethal mutation of the mouse wasted (wst) is a deletion that abolishes expression of a tissue-specific isoform of translation elongation factor 1alpha, encoded by the Eef1a2 gene.

We have identified the mutation responsible for the autosomal recessive wasted (wst) mutation of the mouse. Wasted mice are characterized by wasting and neurological and immunological abnormalities starting at 21 days after birth; they die by 28 days. A deletion of 15.8 kb in wasted mice abolishes expression of a gene called Eef1a2, encoding a protein that is 92% identical at the amino acid level to the translation elongation factor EF1alpha (locus Eef1a). We have found no evidence for the involvement of another gene in this deletion. Expression of Eef1a2 is reciprocal with that of Eef1a. Expression of Eef1a2 takes over from Eef1a in heart and muscle at precisely the time at which the wasted phenotype becomes manifest. These data suggest that there are tissue-specific forms of the translation elongation apparatus essential for postnatal survival in the mouse.

Aging↗
PubMed1997

Mapping in the region of Danforth's short tail and the localization of tail length modifiers.

We have used an interspecific backcross to generate a detailed genetic map around the mouse tail and kidney developmental mutation Danforth's short tail (Sd). The map includes 14 simple sequence repeat (SSR) markers and four genes in a 5-cM region encompassing Sd. In addition we have used a DNA pooling approach to carry out a genome scan to localize quantitative trait loci (QTL) that modify the tail length of Sd progeny of the backcross. This has allowed us to identify a major QTL on chromosome 10 in the region of nodal and three other putative tail length QTL on chromosomes 1, 9, and 18.

Alleles↗
PubMed1996

Genetic and physical mapping of the mouse Ulnaless locus.

The mouse Ulnaless locus is a semidominant mutation which displays defects in patterning along the proximal-distal and anterior-posterior axes of all four limbs. The first Ulnaless homozygotes have been generated, and they display a similar, though slightly more severe, limb phenotype than the heterozygotes. To create a refined genetic map of the Ulnaless region using molecular markers, four backcrosses segregating Ulnaless were established. A 0.4-cM interval containing the Ulnaless locus has been defined on mouse chromosome 2, which has identified Ulnaless as a possible allele of a Hoxd cluster gene(s). With this genetic map as a framework, a physical map of the Ulnaless region has been completed. Yeast artificial chromosomes covering this region have been isolated and ordered into a 2 Mb contig. Therefore, the region that must contain the Ulnaless locus has been defined and cloned, which will be invaluable for the identification of the molecular nature of the Ulnaless mutation.

Animals↗
PubMed1996

Isolation and mapping of novel mouse brain cDNA clones containing trinucleotide repeats, and demonstration of novel alleles in recombinant inbred strains.

Abnormal expansion of trinucleotide repeats (TRs) has now been implicated in the pathogenesis of at least nine human genetic disorders, particularly those in which anticipation and/or fragile sites have been demonstrated. Anticipation, the phenomenon of increasing severity of phenotype in successive generations, has never been seen in species other than man. Nevertheless, animal models for the dynamic mutation of TRs would be extremely valuable. We have screened a mouse brain cDNA library in an attempt to identify clones representing each of the 10 possible classes of trinucleotide repeat. Thirty-seven clones were analyzed in detail. Of the 37 sequences, 18 displayed significant levels of homology with sequences in GenBank, 10 of them with human expressed sequence tags (ESTs). We then analyzed 25 of the clones by PCR of the sequence containing the repeat in a number of different mouse strains and species to assess levels of variability of repeat length. Of the 25 clones analyzed in this way, 64% showed length variation between Mus musculus spp. and Mus spretus, and 32% showed variation between Mus musculus musculus-derived standard laboratory inbred strains. Where variation was detected (17 repeat-containing clones in all), the gene was mapped by linkage analysis. None of the repeats isolated showed any signs of extreme expansion. However, two of the repeats were shown to have undergone size changes during the establishment of a number of recombinant inbred strains, suggesting that these repeats are at least moderately unstable.

Animals↗
PubMed1995

Thirteen genes (Cebpb, E2f1, Tcf4, Cyp24, Pck1, Acra4, Edn3, Kcnb1, Mc3r, Ntsr, Cd40, Plcg1 and Rcad) that probably lie in the distal imprinting region of mouse chromosome 2 are not monoallelically expressed.

Seven imprinted genes are currently known in the mouse but none have been identified yet in the distal imprinting region of mouse Chromosome (Chr) 2, a region which shows striking linkage conservation with human chromosome 20q13. Both maternal duplication/paternal deficiency and its reciprocal for distal Chr 2 lead to mice with abnormal body shapes and behavioural abnormalities. We have tested a number of candidate genes, that are either likely or known to lie within the distal imprinting region, for monoallelic expression. These included 3 genes (Cebpb, E2f1 and Tcf4) that express transcription factors, 2 genes (Cyp24 and Pck1) that are involved in growth, 5 genes (Acra4, Edn3, Kcnb1, Mc3r and Ntsr) where a defect could lead to neurological and probably behavioural problems, and 3 genes (Cd40, Plcg1 and Rcad) that are less obvious candidates but sequence information was available for designing primers to test their expression. On/off expression of each gene was tested by reverse transcription-polymerase chain reaction (RT-PCR) analysis of RNA extracted from tissues of mice with maternal duplication/paternal deficiency and its reciprocal for the distal region of Chr 2. None of the 13 genes is monoallelically expressed in the appropriate tissues before and shortly after birth which suggests that these genes are not imprinted later in development. This study has narrowed down the search for imprinted genes, and valuable information on which genes have been tested for on/off expression is provided. Since there is considerable evidence of conservation of imprinting between mouse and human, we would predict that the 13 genes are not imprinted in human. Five of the genes: E2f1, Tcf4, Kcnb1, Cd40 and Rcad, have not yet been mapped in human. However, because of the striking linkage conservation observed between mouse Chr 2 and human chromosome 20, we would expect these genes to map on human chromosome 20q13.

Alleles↗
PubMed1993

Mapping of the human homologs of the murine paired-box-containing genes.

Mutations in paired-box-containing (Pax) genes have recently been found to be the primary lesions underlying human genetic disorders such as Waardenburg's Syndrome type 1 and mouse developmental mutants such as undulated (un), splotch (Sp), and small eye (Sey). In addition, PAX-6 is a strong candidate gene for aniridia in man. Eight independent Pax genes have been isolated in the mouse. All eight map to distinct regions of the mouse genome; they do not appear to be clustered in the same way as some groups of homeobox-containing genes. We have now mapped the human homologs of all eight of these genes; PAX genes are found on human Chromosomes (Chr) 1, 2, 7, 9, 10, 11, and 20.

Animals↗