scholarly journals Genetic evidence for two t complex tail interaction (tct) loci in t haplotypes.

Genetics ◽  
1989 ◽  
Vol 122 (4) ◽  
pp. 895-903
Author(s):  
J H Nadeau ◽  
D Varnum ◽  
D Burkart
Keyword(s):  
Genetic Analysis ◽  
Tail Length ◽  
Genetic Interactions ◽  
Chromosome 17 ◽  
Wild Type ◽  
T Complex ◽  
Inverted Duplication ◽  
Haplotype A ◽  
Recombination Breakpoints ◽  
T Haplotype

Abstract The t complex on chromosome 17 of the house mouse is an exceptional model for studying the genetic control of transmission ratio, gametogenesis, and embryogenesis. Partial haplotypes derived through rare recombination between a t haplotype and its wild-type homolog have been essential in the genetic analysis of these various properties of the t complex. A new partial t haplotype, which was derived from the complete tw71 haplotype and which is called tw71Jr1, was shown to have unexpected effects on tail length and unique recombination breakpoints. This haplotype, either when homozygous or when heterozygous with the progenitor tw71 haplotype, produced short-tailed rather than normal-tailed mice on certain genetic backgrounds. Genetic analysis of this exceptional haplotype showed that the recombination breakpoints were different from those leading to any other partial t haplotype. Based on this haplotype, a model is proposed that accounts for genetic interactions between the brachyury locus (T), the t complex tail interaction (tct) locus, and their wild-type homolog(s) that determine tail length. An important part of this model is the hypothesis that the tct locus, which enhances the tail-shortening effect of T mutations, is in fact at least two, genetically separable genes with different genetic activities. Genetic analysis of parental and recombinant haplotypes also suggests that intrachromosomal recombination involving an inverted duplicated segment can account for the variable orientation of loci within an inverted duplication on wild-type homologs of the t haplotype.

Identification of a germ-cell-specific transcriptional repressor in the promoter of Tctex-1

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 561-568 ◽  
Author(s):  
M.J. O'Neill ◽  
K. Artzt
Keyword(s):  
Germ Cell ◽  
Gene Family ◽  
Binding Site ◽  
Transcriptional Repressor ◽  
Chromosome 17 ◽  
Wild Type ◽  
Aberrant Expression ◽  
T Complex ◽  
T Haplotype

The Tctex-1 gene family maps to the t complex of the mouse and consists of four copies on chromosome 17 in both wild-type and t-haplotypes. Tctex-1 mRNA is eightfold overexpressed in male and female germ cells in t-haplotype compound heterozygotes (tx/ty). In order to determine the cause of this aberrant expression and the role of this gene family in spermatogenesis and oogenesis it was subjected to extensive molecular analysis. We find that Tctex-1 protein is present in sperm tails and oocytes and that it is present at equal levels in wild-type and t-haplotype testis. Surprisingly, the excess message in t-haplotypes is not translated. Sequence analysis of the gene family reveals that one copy in t-haplotypes has a mutated start codon. This same copy is deleted for a protein-binding motif in its promoter. This motif, GIM (Germ cell Inhibitory Motif) has strong homology to the Xenopus AP-2-binding site but does not appear to be a binding site for mammalian AP-2. A factor(s) present in testis and ovary, but absent in other mouse tissues binds specifically to this site. Transfection assays using Tctex-1 promoter constructs suggest that GIM functions as a transcriptional repressor. The possible role of Tctex-1 in t complex transmission ratio distortion and sterility is discussed.

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

Genetics ◽  
1991 ◽  
Vol 128 (4) ◽  
pp. 799-812 ◽  
Author(s):  
M F Hammer ◽  
S Bliss ◽  
L M Silver
Keyword(s):  
Inbred Strains ◽  
Genetic Exchange ◽  
Transmission Ratio Distortion ◽  
Chromosome 17 ◽  
Wild Type ◽  
T Complex ◽  
Haplotype Allele ◽  
Hybrid Allele ◽  
Paracentric Inversions ◽  
T Haplotype

Abstract 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.

scholarly journals Functional analysis of mutations of murine chromosome 17 with the use of tertiary trisomy.

Genetics ◽  
1991 ◽  
Vol 127 (4) ◽  
pp. 781-788
Author(s):  
A Ruvinsky ◽  
A Agulnik ◽  
S Agulnik ◽  
M Rogachova
Keyword(s):  
Functional Analysis ◽  
Gene Dosage ◽  
Tail Length ◽  
Proximal Region ◽  
The Other ◽  
Chromosome 17 ◽  
Recessive Mutations ◽  
T Complex ◽  
Functional Nature ◽  
Morphogenetic Effects

Abstract Analysis of the functional nature of mutations can be based on comparisons of their manifestation in organisms with a deletion or duplication of a particular chromosome segment. With the use of reciprocal translocation T(16;17)43H, it is feasible to produce mice with tertiary trisomy of the proximal region of chromosome 17. The mutations on chromosome 17 we tested included brachyury (T), hairpin tail (Thp), kinky (Fuki), quaking (qk), tufted (tf), as well as tct (t complex tail interaction), and tcl (t complex lethal) that are specific to t haplotypes. The set of dominant and recessive mutations was assigned to two groups: one obligatory, manifesting itself in the phenotype independently of the number of normal alleles in di- and trisomics, and the other facultative, phenotypically manifesting itself depending upon the dosage of mutant alleles. A model was derived from analysis of the interaction of the T and Thp mutations with t haplotypes. It seeks to explain the morphogenetic effects of the mutations observed in mice of different genotypes. The tir gene is postulated to reside on chromosome 17 within its framework. It is suggested that the gene dosage ratio at the tir and tct loci determines tail length.

scholarly journals Genetic and molecular analysis of the proximal region of the mouse t-complex using new molecular probes and partial t-haplotypes.

Genetics ◽  
1990 ◽  
Vol 126 (4) ◽  
pp. 1103-1114 ◽  
Author(s):  
C A Howard ◽  
G R Gummere ◽  
M F Lyon ◽  
D Bennett ◽  
K Artzt
Keyword(s):  
Wild Mouse ◽  
Molecular Probes ◽  
Proximal Region ◽  
Chromosome 17 ◽  
Lethal Gene ◽  
Strong Linkage Disequilibrium ◽  
Wild Type ◽  
T Complex ◽  
Naturally Occurring ◽  
Normal Transmission

Abstract The t-complex is located on the proximal third of chromosome 17 in the house mouse. Naturally occurring variant forms of the t-complex, known as complete t-haplotypes, are found in wild mouse populations. The t-haplotypes contain at least four nonoverlapping inversions that suppress recombination with the wild-type chromosome, and lock into strong linkage disequilibrium loci affecting normal transmission of the chromosome, male gametogenesis and embryonic development. Partial t-haplotypes derived through rare recombination between t-haplotypes and wild-type homologs have been critical in the analysis of these properties. Utilizing two new DNA probes. Au3 and Au9, and several previously described probes, we have analyzed the genetic structure of several partial t-haplotypes that have arisen in our laboratory, as well as several wild-type chromosomes deleted for loci in this region. With this approach we have been able to further our understanding of the structural and dynamic characteristics of the proximal region of the t-complex. Specifically, we have localized the D17Tul locus as most proximal known in t-haplotypes, achieved a better structural analysis of the partial t-haplotype t6, and defined the structure and lethal gene content of partial t-haplotypes derived from the lethal tw73 haplotype.

scholarly journals Distorter genes of the mouse t-complex impair male fertility when heterozygous

1987 ◽  
Vol 49 (1) ◽  
pp. 57-60 ◽  
Author(s):  
Mary F. Lyon
Keyword(s):  
Male Fertility ◽  
Genetic Background ◽  
Inbred Strains ◽  
Transmission Ratio Distortion ◽  
Chromosome 17 ◽  
Male Mice ◽  
Wild Type ◽  
T Complex ◽  
Ratio Distortion ◽  
Harmful Effects

SummaryMale mice heterozygous for two distorter genes, Tcd-1 and Tcd-2, of the mouse t-complex but homozygous wild type for the responder, were generated by crossing animals carrying the partial t-haplotypes th51 and th18 to inbred strains. The fertility of these males was then compared with that of their brothers carrying normal chromosome 17s. On three of the inbred backgrounds used, C3H/HeH, C57BL/6J and TFH/H, the th51th18 + / + + + males were significantly less fertile than their normal sibs. With the fourth inbred strain used, SM/JH, both types of male were nonnally fertile. This confirmed earlier preliminary findings that when both homologues of chromosome 17 carry wild-type alleles of the responder, heterozygosity for the distorter genes is sufficient to impair fertility, but the effect varies with genetic background. These results are consistent with the concept that both the transmission ratio distortion and the male sterility caused by the t-complex are due to harmful effects of the distorter genes on wild-type alleles of the responder.

scholarly journals t-Specific DNA polymorphisms among wild mice from Israel and Spain.

Genetics ◽  
1988 ◽  
Vol 119 (1) ◽  
pp. 157-160
Author(s):  
F Figueroa ◽  
E Neufeld ◽  
U Ritte ◽  
J Klein
Keyword(s):  
Laboratory Mouse ◽  
The Other ◽  
Dna Polymorphisms ◽  
Chromosome 17 ◽  
Mouse Strains ◽  
Laboratory Mice ◽  
Wild Type ◽  
Wild Mice ◽  
T Complex ◽  
Length Polymorphisms

Abstract Lehrach and his coworkers have isolated a series of DNA probes that specifically hybridize with different regions of mouse chromosome 17 within the t complex. The probes display restriction fragment length polymorphisms, RFLPs, which are specific for the t haplotypes in all laboratory mouse strains tested thus far. Some of these probes have been used to test wild mice populations for these t-associated DNA forms. It is demonstrated that populations from Germany, Switzerland, Italy, Greece, Yugoslavia, Australia, Costa Rica, and Venezuela contain chromosomes in which all the tested DNA loci display the t-specific polymorphisms. The frequency of mice carrying these chromosomes is as high as 31%. Wild mice from Israel and Spain, on the other hand, carry chromosomes displaying t-specific DNA forms only at one or two of the probed loci, while the other loci carry the wild-type (+) forms. These chromosomes thus resemble the partial t haplotypes known from the study of laboratory mice. One possible interpretation of these findings is that these DNA polymorphisms contributed to the assembly of the complete t haplotypes and that these haplotypes may have originated in the Middle East.

scholarly journals NONHOMOLOGOUS PAIRING IN MICE HETEROZYGOUS FOR A t HAPLOTYPE CAN PRODUCE RECOMBINANT CHROMOSOMES WITH DUPLICATIONS AND DELETIONS

Genetics ◽  
1986 ◽  
Vol 113 (3) ◽  
pp. 723-734
Author(s):  
Nora Sarvetnick ◽  
Howard S Fox ◽  
Elizabeth Mann ◽  
Paul E Mains ◽  
Rosemary W Elliott ◽  
...  
Keyword(s):  
Recombination Event ◽  
Genetic Material ◽  
Chromosome 17 ◽  
Structure And Properties ◽  
Wild Type ◽  
Molecular Studies ◽  
Type Form ◽  
Wild Type Form ◽  
T Locus ◽  
T Haplotype

ABSTRACT We have investigated the structure and properties of a chromosomal product recovered from a rare recombination event between a t haplotype and a wild-type form of mouse chromosome 17. Our embryological and molecular studies indicate that this chromosome (twLub  2) is characterized by both a deletion and duplication of adjacent genetic material. The deletion appears to be responsible for a dominant lethal maternal effect and a recessive embryonic lethality. The duplication provides an explanation for the twLub  2 suppression of the dominant T locus phenotype. A reanalysis of previously described results with another chromosome 17 variant called TtOrl indicates a structure for this chromosome that is reciprocal to that observed for twLub  2. We have postulated the existence of an inversion over the proximal portion of all complete t haplotypes in order to explain the generation of the partial t haplotypes twLub  2 and TtOrl. This proximal inversion and the previously described distal inversion are sufficient to account for all of the recombination properties that are characteristic of complete t haplotypes. The structures determined for twLub  2 and TtOrl indicate that rare recombination can occur between nonequivalent genomic sequences within the inverted proximal t region when wild-type and t chromosomes are paired in a linear, nonhomologous configuration.

scholarly journals GENETIC ANALYSIS OF A MOUSE t COMPLEX LOCUS THAT IS HOMOLOGOUS TO A KIDNEY cDNA CLONE

Genetics ◽  
1986 ◽  
Vol 114 (3) ◽  
pp. 993-1006
Author(s):  
Elizabeth A Mann ◽  
Lee M Silver ◽  
Rosemary W Elliott
Keyword(s):  
Cdna Clone ◽  
Chinese Hamster ◽  
Chromosome 17 ◽  
Chromosome 4 ◽  
Wild Type ◽  
Hybrid Analysis ◽  
T Complex ◽  
Proximal Half ◽  
Length Polymorphisms ◽  
Complex Locus

ABSTRACT A mouse kidney cDNA clone, pMK174, identifies restriction fragment length polymorphisms (RFLPs) that map to two unlinked loci. One, designated D17Rp17, has been mapped near quaking, (qk), on chromosome 17 using three sets of recombinant inbred (RI) strains. A study of several t haplotypes resulted in the identification of t-specific alleles of D17Rp17 that map to the proximal half of the t complex. Neither t-specific nor wild-type D17Rp17 alleles are present in chromosomes carrying either the T Orleans (TtOrl) or the T hairpin tail (Thp) deletions. Comparison with other molecular markers indicates that pMK174 identifies a new proximal t complex locus, Rp17. The second locus identified by pMK174, termed D4Rp18, is tentatively assigned to chromosome 4 by mouse-Chinese hamster somatic cell hybrid analysis.

The Putative Oncogene Pim-1 in the Mouse: Its Linkage and Variation Among t Haplotypes

Genetics ◽  
1987 ◽  
Vol 117 (3) ◽  
pp. 533-541
Author(s):  
Joseph H Nadeau ◽  
Sandra J Phillips
Keyword(s):  
Restriction Fragment ◽  
Inbred Mice ◽  
Globin Gene ◽  
Inbred Strains ◽  
Chromosome 17 ◽  
Wild Type ◽  
Alpha Crystallin ◽  
T Complex ◽  
Variant Alleles ◽  
Apparent Association

ABSTRACT Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudoalpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice. There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains. These genes are closely linked within the distal inversion of the t complex. Because it is unlikely that these variants arose independently in t haplotypes and their wild-type homologues, we propose that an exchange of chromosomal segments, probably through double crossingover, was responsible for indistinguishable Pim-1 genes shared by certain t haplotypes and their wild-type homologues. There was, however, no apparent association between variant alleles of these three genes among t haplotypes as would be expected if a single exchange introduced these alleles into t haplotypes. If these variant alleles can be shown to be identical to the wild-type allele, then lack of association suggests that multiple exchanges have occurred during the evolution of the t complex.

scholarly journals New molecular markers for the distal end of the t-complex and their relationships to mutations affecting mouse development.

Genetics ◽  
1992 ◽  
Vol 131 (1) ◽  
pp. 175-182 ◽  
Author(s):  
T Ebersole ◽  
F Lai ◽  
K Artzt
Keyword(s):  
Molecular Markers ◽  
Mouse Chromosome ◽  
Length Polymorphism ◽  
Rflp Analysis ◽  
Chromosome 17 ◽  
Cosmid Library ◽  
Sequence Length ◽  
Mouse Development ◽  
T Complex ◽  
T Haplotype

Abstract Many mutations affecting mouse development have been mapped to the t-complex of mouse chromosome 17. We have obtained 17 cosmid clones as molecular markers for this region by screening a hamster-mouse chromosome 17 and 18 cell hybrid cosmid library with mouse-specific repetitive elements and mapping positive clones via t-haplotype vs. C3H restriction fragment length polymorphism (RFLP) analysis. Twelve of the clones mapping distal to Leh66B in t-haplotypes are described here. Using standard RFLP analysis or simple sequence length polymorphism between t-haplotypes, exceptional partial t-haplotypes and nested sets of inter-t-haplotype recombinants, five cosmids have been mapped in or around In(17)3 and seven in the most distal inversion In17(4). More precise mapping of four of the cosmids from In(17)4 shows that they will be useful in the molecular identification of some of the recessive lethals mapped to the t-complex: two cosmids map between H-2K and Crya-1, setting a distal limit in t-haplotypes for the position of the tw5 lethal, one is inseparable from the tw12 lethal, and one maps distal to tf near the t0(t6) lethal and cld.

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