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L M Silver

Publications and source records attributed to L M Silver.

At least 73 records · Page 4Linked to original sources
PubMed1993

The human homolog of a candidate mouse t complex responder gene: conserved motifs and evolution with punctuated equilibria.

The mouse Tcp-10 gene has been established as a molecular candidate for the t complex responder locus which plays a central role in the transmission ratio distortion phenotype expressed by males heterozygous for a t haplotype. Here we describe a comparison of the mouse and human TCP10 coding sequences. The results show that whole exons have been added or eliminated from the transcripts expressed in each species, suggesting an evolutionary process of punctuated equilibria for this gene. Two of the polypeptide regions that are most conserved between the two species contain specific peptide motifs. The conserved C-terminal region contains a unique nonapeptide repeat of unknown function and the conserved N-terminal region contains a pair of leucine zippers within a region that shows additional similarity to the coiled-coil regions of various cytosolic polypeptides. These results are discussed in terms of the possible function of the TCP10 protein.

Amino Acid Sequence↗
PubMed1993

Phylogenetic analysis of the alpha-globin pseudogene-4 (Hba-ps4) locus in the house mouse species complex reveals a stepwise evolution of t haplotypes.

A parsimony analysis was performed on restriction sites at the Hba-ps4 pseudogene locus within one of four inversions associated with mouse t haplotypes. The results suggest that all t haplotypes form a monophyletic group and that the in (17)4 inversion originated before the radiation of the Mus musculus species complex but after the divergence of the lineages leading to M. spretus, M. abbotti, and M. hortulanus. A time frame based on the evolutionary rate of mouse pseudogenes places the origin of this t haplotype inversion at 1.5 Mya, or approximately 1.5 Myr after the origin of the more proximal t complex inversion, in (17)2. The accumulated evidence indicates that complete t haplotypes have been assembled in a stepwise manner, with each of these inversions occurring on separate chromosomal lineages and at different evolutionary times. In addition, the evolutionary relationships of pseudogene sequences resulting from genetic exchange between wild-type and t haplotype alleles were examined. Analysis of sequences from the 5' and 3' sides of a putative site of recombination resulted in cladograms with different topologies. The implications for hypotheses concerning the evolutionary forces acting on t haplotypes and their rapid propagation throughout worldwide populations of mice are discussed.

Alleles↗
PubMed1993

Factors that may regulate assembly of the mammalian sperm tail deduced from a mouse t complex mutation.

A unique pattern of aberrant sperm development occurs in laboratory mice (Mus domesticus) that have been made homozygous for an allele of an autosomal gene, Hst-6s, derived from another mouse species, Mus spretus. During the abnormal spermiogenic process of these sterile animals, the sperm tail fails to assemble normally, although a bud develops at the site of the centriole in early spermatids. The bud enlarges during sperm development and eventually contains elements of a mature sperm tail. Tubulin assembles primarily into single microtubules rather than doublets. These singlets form a circular array that is not oriented relative to the centriole. While dense fibers form in association with the singlet microtubules, the fibrous sheath components accumulate in a single irregular mass. These observations suggest that microtubule doublets are required for the organization of an axoneme. In addition, while dense fibers can form normally in association with singlet microtubules, the fibrous sheath requires the axoneme as a substrate for normal organization.

Animals↗
PubMed1992

Distortion of transmission ratio by a candidate t complex responder locus transgene.

The mouse t complex responder locus (Tcr) is centrally involved in the phenomenon of male-specific transmission ratio distortion (TRD) through its action in haploid germ cells. Previously, we identified a candidate gene, Tcp-10b, whose t allele generates alternatively spliced transcripts. The full-length Tcp-10bt transcript is present in pre- and postmeiotic germ cells and encodes a product that is virtually identical with that encoded by the wild-type allele. The alternatively spliced t-specific transcript is observed in post-meiotic haploid spermatids and would encode an altered polypeptide that could convey the Tcrt phenotype. To assess their function, we have introduced constructs representing each Tcp-10bt transcript into transgenic mice. Breeding experiments demonstrate that these two constructs alter the transmission ratios of t haplotypes from male mice, but in opposite directions. The results provide support for the hypothesis that Tcp-10bt is a component of the Tcr locus.

Animals↗
PubMed1992

Localization of the Mas proto-oncogene to a densely marked region of mouse chromosome 17 associated with genomic imprinting.

The mouse homolog of the human proto-oncogene MAS was mapped by two interspecific backcrosses to the proximal portion of MMU17. Higher resolution mapping was accomplished through the analysis of genotypes duplicated or deleted for a megabase-size subregion within MMU17. The results demonstrate a map position for Mas in the close vicinity of Igf2r, which encodes another membrane receptor known to undergo genomic imprinting. The data provide further evidence for the clustering of genes in a 1-Mb region of chromosome 17, with the absence of any identified genes in a nearby region likely to be six times larger.

Animals↗
PubMed1992

Genetic mapping of three human homologues of murine t-complex genes localizes TCP10 to 6q27, 15 cM distal to TCP1 and PLG.

Human homologues of mouse t-complex genes have been cloned and localized physically to chromosome 6p or 6q. TCP1, TCP10, and PLG are human homologues of genes located in the proximal portion of the t-complex on mouse chromosome 17. We present here results of genetic mapping of these human t-complex homologues previously localized to 6q25-q27, 6q21-q27, and 6q26-q27, respectively, by physical techniques. TCP1 and PLG do not recombine with each other and are separated from TCP10 by about 15 cM, while the corresponding mouse genes are no more than 4 cM apart. Genetic mapping with markers well localized cytogenetically places TCP1 and PLG proximal to TCP10 and localizes the latter to the cytogenetic band 6q27. It is likely that the organization of human t-complex homologues on 6q is similar to that of t haplotypes rather than that of wildtype murine chromosome 17.

Animals↗
PubMed1992

Concerted evolution of the mouse Tcp-10 gene family: implications for the functional basis of t haplotype transmission ratio distortion.

The mouse Tcr locus is defined by its central role in the transmission ratio distortion phenotype characteristic of t haplotypes. A molecular candidate for Tcr has been identified in the form of a gene--Tcp-10b--expressed during spermatogenesis. Tcp-10b is one member of a multigene family present in two to four copies on different homologs of chromosome 17. The coding regions of the Tcp-10 genes present within two inbred strains were compared with those of the tw5 haplotype. The various gene family members are highly conserved relative to each other with a minimum nucleotide identity of 98.6% in all pairwise comparisons. Maximal parsimony analysis indicates that the Tcp-10 gene family has evolved in a concerted manner with the obliteration of nearly all individual gene-specific characteristics. As a consequence, the candidate for the full-length mutant Tcr gene product is distinguished by only a single, highly conservative, amino acid change. The data are consistent with the hypothesis that the effector of mutant Tcr activity is a second, alternatively spliced product that is expressed in a haploid- and allele-specific manner.

Alleles↗
PubMed1991

Allele- and haploid-specific product generated by alternative splicing from a mouse t complex responder locus candidate.

Mouse t haplotypes represent a variant form of chromosome 17 that has evolved the ability to propagate through natural populations by the phenomenon of 'transmission ratio distortion' (TRD), in which heterozygous +/t males transmit their t-carrying chromosome to 95% or more of their offspring. Although multiple t-associated loci have a role in expression of this phenotype, only one--the t complex responder (Tcr) locus--is responsible for determining which of the two homologues of chromosome 17 will be transmitted at a high ratio. A candidate gene (Tcp-10b) for Tcr that is expressed in both meiotic and post-meiotic male germ cells has been cloned. But for this candidate gene to function as the haploid effector of TRD, the t-allele of this gene (Tcp-10bt) must express a unique product in a haploid-specific manner. Here we show that a change in the splicing pattern of Tcp-10bt transcripts occurs during sperm differentiation. This change results in a unique allele-specific and haploid-specific transcript which could encode a variant polypeptide that would fulfil the conditions required of the Tcr effector of TRD.

Alleles↗
PubMed1991

Two-dimensional gel analysis of complex DNA families: methodology and apparatus.

We describe a reproducible protocol for the analysis of individual members of complex mammalian gene families by gel fractionation in two dimensions within a specially designed, easily built electrophoretic apparatus. We have used this protocol to resolve the family of mouse H-2 class I genes, with approximately 30 members, as well as two different families of endogenous retroviral-like sequences, each of which has approximately 180 members dispersed throughout the genome. The results demonstrate the feasibility of using this protocol for rapid, whole genome analysis of individual animals and cell lines. Two-dimensional DNA analysis of highly repeated retroviral-like DNA families could be applied to genetic mapping and cloning experiments as well as to obtaining whole genome fingerprints in the analysis of somatic cell hybrid lines that contain a subset of chromosomes from the genome of interest.

DNA Restriction Enzymes↗
PubMed1991

Genetic exchange across a paracentric inversion of the mouse t complex.

Mouse t haplotypes are distinguished from wild-type forms of chromosome 17 by four nonoverlapping paracentric inversions which span a genetic distance of 20 cM. These inversion polymorphisms are responsible for a 100-200-fold suppression of recombination which maintains the integrity of complete t haplotypes and has led to their divergence from the wild-type chromosomes of four species of house mice within which t haplotypes reside. As evidence for the long period of recombinational isolation, alleles that distinguish all t haplotypes from all wild-type chromosomes have been established at a number of loci spread across the 20-cM variant region. However, a more complex picture emerges upon analysis of other t-associated loci. In particular, "mosaic haplotypes" have been identified that carry a mixture of wild-type and t-specific alleles. To investigate the genetic basis for mosaic chromosomes, we conducted a comprehensive analysis of eight t complex loci within 76 animals representing 10 taxa in the genus Mus, and including 23 previously characterized t haplotypes. Higher resolution restriction mapping and sequence analysis was also performed for alleles at the Hba-ps4 locus. The results indicate that a short tract of DNA was transferred relatively recently across an inversion from a t haplotype allele of Hba-ps4 to the corresponding locus on a wild-type homolog leading to the creation of a new hybrid allele. Several classes of wild-type Hba-ps4 alleles, including the most common form in inbred strains, appear to be derived from this hybrid allele. The accumulated data suggest that a common form of genetic exchange across one of the four t-associated inversions is gene conversion at isolated loci that do not play a role in the transmission ratio distortion phenotype required for t haplotype propagation. The implications of the results pose questions concerning the evolutionary stability of gene complexes within large paracentric inversions and suggest that recombinational isolation may be best established for loci residing within a short distance from inversion breakpoints.

Animals↗
PubMed1991

A novel mouse chromosome 17 hybrid sterility locus: implications for the origin of t haplotypes.

The effects of heterospecific combinations of mouse chromosome 17 on male fertility and transmission ratio were investigated through a series of breeding studies. Animals were bred to carry complete chromosome 17 homologs, or portions thereof, from three different sources-Mus domesticus, Mus spretus and t haplotypes. These chromosome 17 combinations were analyzed for fertility within the context of a M. domesticus or M. spretus genetic background. Two new forms of hybrid sterility were identified. First, the heterospecific combination of M. spretus and t haplotype homologs leads to complete male sterility on both M. spretus and M. domesticus genetic backgrounds. This is an example of symmetrical hybrid sterility. Second, the presence of a single M. domesticus chromosome 17 homolog within a M. spretus background causes sterility, however, the same combination of chromosome 17 homologs does not cause sterility within the M. domesticus background. This is a case of asymmetrical hybrid sterility. Through an analysis of recombinant chromosomes, it was possible to map the M. domesticus, M. spretus and t haplotype alleles responsible for these two hybrid sterility phenotypes to the same novel locus (Hybrid sterility-4). Previous structural studies had led to the hypothesis that the ancestral t haplotype originated through an introgression event from M. spretus or a related species. If this were true, one might expect that (1) M. spretus homologs would be transmitted at a non-Mendelian ratio within the M. domesticus background, and (2) t haplotypes would be transmitted at a ratio closer to Mendelian within the M. spretus background.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗