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Results for “Enhancer mapping”

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PubMed1993

The human C/EBP delta (CRP3/CELF) gene: structure and chromosomal localization.

In an attempt to identify C/EBP-like transcription factors expressed in the prostate, a cDNA homologous to the mouse C/EBP delta (CRP3) and the rat CELF gene was isolated. A genomic clone containing the entire C/EBP delta gene was isolated using a cDNA fragment as a probe. The gene was characterized by restriction mapping and sequence analysis. By fluorescence in situ hybridization, using the biotinylated genomic clone as a probe, the C/EBP delta gene was assigned to the pericentromeric region of human chromosome 8, most probably to 8q11. This chromosomal localization was confirmed by analysis of a panel of human x hamster somatic cell hybrid DNA samples with a C/EBP delta-specific STS. As a result, the C/EBP delta gene could be positioned between the PLAT and the MOS loci.

Amino Acid Sequence↗

PubMed1998

A novel E box/AT-rich element is required for muscle-specific expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene.

The cardiac/slow twitch sarcoplasmic reticulum (SR) Ca2+-ATPase gene (SERCA2 ) encodes a calcium transport pump whose expression is regulated in a tissue- and development-specific manner. Previously we have identified two distinct positive regulatory regions (bp -284 to -72 and -1815 to -1105) as important for SERCA2 promoter activity. Here we demonstrate that the SERCA2 distal promoter region functions like an enhancer by activating a heterologous promoter (TK) in a muscle cell-specific manner. Through deletion analysis a core enhancer region was delimited to the -1467 to -1105 bp fragment. We identified the E box/AT-rich element located at -1115 bp as critical for maximal enhancer activity. Gel mobility shift studies revealed that this E box/AT-rich element specifically binds a protein which is induced during Sol8 myogenesis. This region includes two other cis -acting elements, CArG and MCAT, which also bind specific nuclear protein complexes from Sol8 myotubes. Mutagenesis of each of these sites resulted in decreased SERCA/TK-CAT promoter activity. Based on these data, we propose that the E box/AT-rich element may contribute along with CArG and MCAT elements to the overall activation and regulation of the SERCA2 gene promoter.

3T3 Cells↗

PubMed1988

Functional mapping of Autographa california nuclear polyhedrosis virus genes required for late gene expression.

A plasmid containing the bacterial chloramphenicol acetyltransferase (CAT) gene under the control of an Autographa california nuclear polyhedrosis virus (AcNPV) late gene promoter was constructed. This plasmid (pL2cat) also contained the AcNPV hr5 enhancer element. Transient-expression assay experiments indicated that the late promoter was active in Spodoptera frugiperda cells cotransfected with pL2cat and AcNPV DNA but not when pL2cat was transfected alone. Low levels of CAT activity were observed in cells cotransfected with pL2cat and pIE-1 DNAs. However, CAT activity was not induced in a similar plasmid which lacked the cis-linked enhancer element, indicating that the enhancer was required for expression of the late gene. Cotransfection mapping of pPstI clones of AcNPV DNA indicated that the pPstI-G clone of viral DNA contained a factor which further stimulated late gene expression 3- to 10-fold. Transient-expression assay analysis of subclones of pPstI-G localized the trans-active factor to a 3.0-kilobase XbaI fragment. The nucleotide sequence of this fragment was determined and found to contain three potential open reading frames. A computer-assisted search of a protein database revealed no closely related proteins. One of the predicted amino acid sequences contained potential metal-binding domains similar to those found in nucleic acid-binding proteins. Subcloning and subsequent CAT assay indicated that two of the open reading frames were required for the activation of pL2cat. Nuclease S1 mapping of infected and transfected RNAs indicated that the two open reading frames were transcribed as delayed-early genes. Quantitative nuclease S1 analysis and differential DNA digestion of recovered plasmids indicated that the activation of pL2cat was not due to an increase in steady-state levels of mRNA replication of the viral DNA.

Amino Acid Sequence↗

PubMed1995

Stimulation of mitogen-activated protein kinase by thyrotropin in astrocytes.

We have recently reported the expression of the thyrotropin (TSH) receptor and the stimulation by TSH of type-II iodothyronine 5'-deiodinase in astrocytes. In these cells, TSH stimulated arachidonate release, but neither cAMP production, nor phosphatidylinositolbisphosphate hydrolysis, as described in the human thyroid gland. Here we report, in contrast to a recent observation made in dog thyroid cells, that TSH stimulates mitogen-activated protein kinase (MAP kinase) in astrocytes. Indeed, TSH increases the tyrosine phosphorylation of the two isoforms of MAP kinase expressed in these cells, in correlation with both a slower electrophoretic migration of the tyrosine phosphorylated species and an enhanced enzymic activity measured on a specific substrate peptide. This stimulation of MAP kinase by TSH was specifically inhibited by incubation of astrocytes in the presence of human blocking anti-(TSH receptor) IgG, and by immunoprecipitation of TSH with monoclonal anti-TSH IgG. In astrocytes, TSH was neither mitogenic by itself, nor modified significantly the basic-fibroblast-growth-factor-induced mitogenesis. The stimulation of MAP kinase by TSH was not affected by treatment with pertussis toxin, suggesting guanine-nucleotide-binding-regulatory protein i/o was not implicated in this TSH effect. Our model will allow the study of the stimulation of MAP kinase by TSH without interference either from cAMP or from phosphoinositide signalling pathways.

Animals↗

PubMed1998

Integrin-mediated adhesion and signalling in ovarian cancer cells.

The integrins are a family of cell surface receptors which mediate cellular adhesion and signalling events. Our goal was to evaluate integrin function and signalling pathways in ovarian cancer cells. Ovarian cancer cell lines, NIH:OVCAR-3 and NIH:OVCAR-5, exhibited distinct extracellular matrix (ECM) binding preferences which were mediated primarily through beta1 integrin interactions. Western blot analysis was used to identify changes in cellular phosphotyrosine, focal adhesion kinase (FAK) and mitogen activated protein (MAP) kinase. Tyrosine phosphorylation of integrin-associated phosphoproteins was not enhanced in either cell type in response to adhesion onto ECM components or receptor crosslinking. FAK expression was greater in NIH:OVCAR-5 cells while MAP kinase activity was higher in NIH:OVCAR-3 cells. The data suggest that these two ovarian cancer cell lines exhibit specific ECM binding preferences and distinct differences in phosphotyrosine, focal adhesion and MAP kinase expression profiles.

Antigens, CD↗

PubMed1994

Interactive roles of Ras, insulin receptor substrate-1, and proteins with Src homology-2 domains in insulin signaling in Xenopus oocytes.

Insulin receptor substrate-1 (IRS-1) serves as the major immediate substrate of insulin/insulin-like growth factor (IGF)-1 receptors and following tyrosine phosphorylation binds to specific Src homology-2 (SH2) domain-containing proteins including the p85 subunit of phosphatidylinositol (PI) 3-kinase and GRB2, a molecule believed to link IRS-1 to the Ras pathway. To investigate how these SH2-containing signaling molecules interact to regulate insulin/IGF-1 action, IRS-1, glutathione S-transferase (GST)-SH2 domain fusion proteins and Ras proteins were microinjected into Xenopus oocytes. We found that pleiotropic insulin actions are mediated by IRS-1 through two independent, but convergent, pathways involving PI 3-kinase and GRB2. Thus, microinjection of GST-fusion proteins of either p85 or GRB2 inhibited IRS-1-dependent activation of mitogen-activated protein (MAP) and S6 kinases and oocyte maturation, although only the GST-SH2 of p85 reduced insulin-stimulated PI 3-kinase activation. Co-injection of a dominant negative Ras (S17N) with IRS-1 inhibited insulin-stimulated MAP and S6 kinase activation. Micro-injection of activated [Arg12,Thr59]Ras increased basal MAP and S6 kinase activities and sensitized the oocytes to insulin-stimulated maturation without altering insulin-stimulated PI 3-kinase. The Ras-enhanced oocyte maturation response, but not the elevated basal level of MAP and S6 kinase, was partially blocked by the SH2-p85, but not SH2-GRB2. These data strongly suggest that IRS-1 can mediate many of insulin's actions on cellular enzyme activation and cell cycle progression requires binding and activation of multiple different SH2-domain proteins.

Adaptor Proteins, Signal Transducing↗

PubMed1990

Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1.

The homeodomain-containing transcription factor hepatocyte nuclear factor 1 (HNF-1) most likely plays an essential role during liver organogenesis by transactivating a family of greater than 15 predominantly hepatic genes. We have isolated cDNA clones encoding mouse HNF-1 and expressed them in monkey COS cells and in the human T-cell line Jurkat, producing HNF-1 DNA-binding activity as well as transactivation of reporter constructs containing multimerized HNF-1 binding sites. In addition, the HNF-1 gene was assigned by somatic cell hybrids and recombinant inbred strain mapping to mouse chromosome 5 near Bcd-1 and to human chromosome 12 region q22-qter, revealing a homologous chromosome region in these two species. The presence of HNF-1 mRNA in multiple endodermal tissues (liver, stomach, intestine) suggests that HNF-1 may constitute an early marker for endodermal, rather than hepatocyte, differentiation. Further, that HNF-1 DNA-binding and transcriptional activity can be conferred by transfecting the HNF-1 cDNA into several cell lines indicates that it is sufficient to activate transcription in the context of ubiquitously expressed factors.

Amino Acid Sequence↗

PubMed1988

The HBV X-ORF encodes a transactivator: a potential factor in viral hepatocarcinogenesis.

We report here on a transactivating function of HBV DNA. The effect is shown by stimulation of transient expression of pSV2cat DNA in cotransfected human liver CCL13 cells. Transfection experiments with plasmid constructs containing different HBV DNA fragments and Northern analyses of RNA from cells transfected with these recombinant plasmids indicate that a transactivating function is encoded within the X-ORF. A frameshift mutation within the X gene causes loss of activity thus demonstrating requirement of a protein. The increase in the level of CAT-specific RNA suggests that the transactivation is by transcriptional enhancement. Constitutive expression of the transactivator function was also observed in cells stably transfected with HBV DNA. A number of eukaryotic promoters, SV40-early, HSV-TK, HTLV-I and RSV LTRs were responsive to transactivation by HBV DNA. However, the MMTV LTR and the human metallothionein promoter (MTIIA) were considerably less responsive than the others. The transactivational potential of HBV DNA was much higher in human cells and cells of higher primates than in rodent cells, thereby indicating interacting cellular factors. These results introduce additional considerations for the role of HBV in the development of hepatocellular tumors.

Acetyltransferases↗

PubMed1999

Contrast angiosonography: a technology to improve Doppler ultrasound examinations of the prostate.

OBJECTIVES: A feasibility study to evaluate whether analysis techniques adapted from X-ray angiography can be used to analyze the transient enhancement of prostate blood flow patterns in color Doppler maps as obtained after administering ultrasound contrast agents. METHODS: Injections of ultrasound contrast agents were given to dogs and humans, and color Doppler blood flow patterns in fixed transverse sections through the prostate were recorded on video tape. Computer assistance of Doppler signals over time is used to evaluate the transient enhancement of flow patterns obtained with contrast-enhanced Doppler ultrasound. Results are compared to indicator dilution curve theory as used in, e.g., X-ray angiography. RESULTS: Administering a contrast agent to improve color Doppler evaluation of prostate blood flow resulted in clear enhancement of Doppler signal intensities without unwanted side effects. Using the computer, the perfused area of the prostate could be obtained quantitatively over time showing profiles of individual heartbeats. Averaging the perfused area over one heartbeat resulted in an indicator dilution curve, and correlation with dilution theory indicated the feasibility of applying wash-in and wash-out analysis of contrast agents in color Doppler images. CONCLUSION: Frame-by-frame interpretation by the computer indicated the feasibility of analyzing the transient enhancement of blood flow visibility in the Doppler image over time using techniques such as wash-in and wash-out time. This technology provides researchers in the field of ultrasound evaluation of the prostate the opportunity to apply a new diagnostic tool, contrast angiosonography, in their research. This method for analysis of prostatic blood flow can be helpful in any application that affects the blood supply of the prostate such as heat treatments and hormonal treatments.

Aged↗

PubMed2006

Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region.

Anti-Smith (anti-Sm) autoantibodies are directed to proteins in the small-nuclear ribonucleoprotein (snRNP) family and are considered specific for systemic lupus erythematosus (SLE) in both humans and mice. We previously established that NOD.c3c4 mice, carrying B6 and B10 congenic segments from chromosomes 3 to 4 on an nonobese diabetic (NOD) background, and NOD.Idd9R28 mice, carrying a B10 segment on c4 alone, developed significant penetrance of anti-Sm antibody production. Here we determine autoantibody incidence in additional NOD.Idd9 congenic strains and use a congenic mapping approach to narrow the interval necessary for enhanced autoantibody production to a approximately 5.6-Mb region containing insulin-dependent diabetes (Idd)9.3. The Idd9.3 interval contains the candidate molecule cluster of differentiation (CD)137, which is a member of the tumor necrosis factor (TNF) receptor superfamily, functions as an inducible costimulator of T cells, and controls T-B interactions. The NOD and B10 CD137 alleles have sequence polymorphisms and different functional effects on T cells; the NOD CD137 allele mediates weaker T cell proliferative responses and decreased interleukin (IL)-2 production after CD137-mediated costimulation. Our work establishes CD137 as a candidate gene for control of autoantibody production in NOD.Idd9.3 congenic mice.

Animals↗

PubMed1999

Integrating neuromorphic action-oriented perceptual inputs to generate a navigation behaviour for a robot.

We use neural networks with pointer map architectures to provide simple attentional processing in a robotic task. A pointer map comprises a map of neurons that encode a stimulus. Besides global feedback inhibition, the map receives feedback excitation via a small group of pointer neurons that encode the location of a salient stimulus on the map as a vectorial representation. The pointer neurons are able to apply selective processing to a particular region of the network. The robot uses these properties to manoeuver in relation to an attended object. We implemented a controller composed of two pointer maps, and a motor map. The first pointer map reports the direction of a salient obstacle in a one-dimensional map of distance derived from infrared sensors. The second pointer map reports the direction to potential obstacles in a two-dimensional edge-enhanced image derived from a forward looking CCD-camera. These outputs are applied to a motor map, where they bias the motor control signals issued to the robots wheels, according to navigational intentions.

Avoidance Learning↗

PubMed1991

[Modification of stereotypy-producing and ambulation-increasing effects following repeated administration of methamphetamine in rats].

Effects of repeated administration of methamphetamine (MAP: 1.25, 2.5 and 5 mg/kg, sc) at an interval of 4 days for 10 times on stereotyped behaviors as well as ambulatory activity in adult male rats of Wistar strain were investigated. In the first administration of MAP 1.25 mg/kg, marked ambulation-increasing effect was observed mixing with simple stereotyped behaviors such as sniffing and head-bobbing. The stereotypy-producing effect of MAP was apparently observed in a dose-dependent manner, and complicated stereotyped behaviors such as head-weaving and licking simultaneously with sniffing and head-bobbing were frequently demonstrated when 5 mg/kg of MAP was first administered. Furthermore, the ambulation-increasing effect after the drug showed biphasic pattern, i.e. pre-stereotypic and post-stereotypic increases in ambulatory activity, because the activity was interfered by the stereotyped behaviors. When MAP was administered repeatedly, the sniffing- and head-bobbing-producing effects were selectively enhanced at any dose, showing sensitization phenomenon (reverse tolerance), and the pre-stereotypic increase in ambulatory activity was inhibited, while the post-stereotypic increase was progressively enhanced. Although the sensitized stereotypy-producing effect was observed more markedly in the 10th administration of MAP 2.5 mg/kg than that in the first administration of MAP 5 mg/kg, the complicated stereotyped behaviors were hardly seen. It is suggested that the sensitization effects are not always identical qualitatively with the effects observed after increase in MAP-dose.

Animals↗

PubMed2004

Nicotinic enhancement of proliferation in bovine and porcine cerebral microvascular endothelial cells.

Nicotinic acetylcholine receptors are found in microvascular endothelial cells. To reveal the functional role in cerebral angiogenic processes, we studied the nicotinic modulation of proliferation activity in cultured bovine and porcine cerebral microvascular endothelial cells. The proliferation activity was determined by an increase in the number of cells present in culture dishes. When the bovine cerebral endothelial cells at different passages were cultured in the presence of nicotine (10 nM), the proliferation activities were significantly increased in the cells at passage 1 and passage 3, but not at passage 4. Reverse transcriptase-polymerase chain reaction studies demonstrated that the expression of mRNAs coding for alpha3 nicotinic receptor subunit was significantly reduced in the bovine cerebral endothelial cells at passage 4, compared with that at passage 1. The proliferation of porcine cerebral endothelial cells (passage 1) was enhanced by acetylcholine (10 nM-100 microM) in the presence of atropine, a muscarinic antagonist, and this enhancing effect was inhibited by hexamethonium (100 microM, a nicotinic antagonist). The stimulation by acetylcholine (1 microM, with atropine) or nicotine (10 nM) induced the phosphorylation of a mitogen-activated protein (MAP) kinase (extracellular-signal regulated kinase: ERK) in the serum-starved endothelial cells. In the presence of PD98059 (2 microM, a MAP kinase kinase inhibitor) and atropine, acetylcholine (1 microM) failed to enhance the proliferation of porcine cerebral endothelial cells. These results demonstrate that nicotinic stimulation promotes the proliferation of bovine and porcine cerebral microvascular endothelial cells, at least in part, through the MAP kinase activation.

Animals↗

PubMed1998

Silencer and enhancer regions in the human CD95 (Fas/APO-1) gene with sequence similarity to the granulocyte-macrophage colony-stimulating factor promoter: binding of single strand-specific silencer factors and AP-1 and NF-AT-like enhancer factors.

The CD95 (Fas/APO-1) apoptosis receptor is expressed in a variety of tissues and transiently upregulated in lymphocytes during activation-induced cell death. A silencer (S1; -1035 to -1008) and an adjacent enhancer (E1; -1007 to -964) region have been mapped in the CD95 gene. The S1 region shows similarity to binding sites for the transcriptional repressor NF-GMb, which prefers binding to single-stranded DNA. The E1 contains an everted repeat of two CATTA/T elements spaced by 2 bp (ER2). Such motifs are directly repeated in the CLE0 region of the human granulocyte-macrophage colony-stimulating factor (huGM-CSF) promoter. A motif (TGATGTCA) which matches a CREB site and is similar to an AP-1 site is embedded within ER2. Sequence-specific binding of nuclear factors to single-stranded S1 probes involved, to some extent, a central heptamer motif (ATCCAAA) also present in E1. Competition binding studies suggested that AP-1 or AP-1 components, as well as factors related, but not identical, to NF-AT bound to E1 probes. S1-binding-proteins/complexes of 47, 77, and 100 kDa were detected by Southwestern analysis and ultraviolet crosslinking. Complexes of 70 and 80 kDa were formed with a double-stranded E1 probe in UV-crosslinking, whereas Southwestern analysis with this probe revealed single binding species of 59 and 113 kDa. ER2 autonomously enhanced transcription from the heterologous HSV tk promoter in a cell type-specific manner only in the absence of the S1 region. This analysis has identified a small region in the CD95 gene containing adjacent opposing regulatory elements which are likely to be involved in the cell type- and activation state-specific gene expression under physiologic conditions.

Animals↗

PubMed1986

Endocardial catheter mapping: validation of a cineradiographic method for accurate localization of left ventricular sites.

To guide surgical therapy for ventricular tachycardia by preoperative endocardial catheter mapping, accurate anatomic localization of arrhythmogenic sites is mandatory. For this reason we developed a mathematical cineradiographic method to compute left ventricular sites relative to three anatomic reference points: the centers of aortic and mitral valve ostia and the left ventricular apex. To validate the method 14 epicardial left ventricular markers were implanted in four dogs to simulate arrhythmogenic sites. Distances between markers and the anatomic references were calculated and the results were compared with postmortem measurements. The difference between calculated and measured distances was 0.5 +/- 3.1 mm (mean +/- SD), confirming accurate localization of anatomic marker sites. However, in surgery the results have to be displayed in a practically applicable, unambiguous way. Therefore, wire skeletons were constructed to represent calculated endocardial marker sites relative to the anatomic reference points. To validate this approach, 14 markers were implanted in the left ventricular subendocardium in four dogs. Wire skeletons were constructed, one for each marker site, and inserted postmortem into the left ventricular cavity via a 2 cm incision. In all cases the correct indication of a marker site by the corresponding wire skeleton was confirmed by fluoroscopic inspection in multiple projections. This wire skeleton technique may enhance the practical usefulness of preoperative endocardial catheter mapping.

Animals↗

PubMed1995

Overexpression of epsilon-protein kinase C enhances nerve growth factor-induced phosphorylation of mitogen-activated protein kinases and neurite outgrowth.

Protein kinase C (PKC) activation enhances neurite outgrowth in several cell lines and primary neurons. The PKC isozymes that mediate this response are unknown. One clue to their identity has come from studies using PC12 cells treated with ethanol. In these cells, ethanol increases levels of delta-PKC and epsilon-PKC and markedly enhances nerve growth factor (NGF)-induced neurite outgrowth and activation of mitogen-activated protein (MAP) kinases by a PKC-dependent mechanism. Since these findings suggest that delta-PKC or epsilon-PKC can promote neural differentiation, we studied neurite outgrowth in stably transfected PC12 cell lines that overexpress these isozymes. Overexpression of epsilon-PKC markedly increased NGF-induced neurite outgrowth. This effect was blocked by down-regulating PKC or by treating cells with the PKC inhibitor GF 109203X. In addition, overexpression of epsilon-PKC enhanced NGF-induced phosphorylation of MAP kinases. In contrast, overexpression of delta-PKC did not alter responses to NGF. These results demonstrate that epsilon-PKC promotes NGF-induced neurite outgrowth by enhancing NGF signal transduction. These findings suggest a role for epsilon-PKC in neural differentiation and plasticity.

Amino Acid Sequence↗

PubMed1992

Glucocorticoid receptor-mediated suppression of the interleukin 2 gene expression through impairment of the cooperativity between nuclear factor of activated T cells and AP-1 enhancer elements.

The immunosuppressant hormone dexamethasone (Dex) interferes with T cell-specific signals activating the enhancer sequences directing interleukin 2 (IL-2) transcription. We report that the Dex-dependent downregulation of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and calcium ionophore-induced activity of the IL-2 enhancer are mediated by glucocorticoid receptor (GR) via a process that requires intact NH2- and COOH-terminal and DNA-binding domains. Functional analysis of chloramphenicol acetyltransferase (CAT) vectors containing internal deletions of the -317 to +47 bp IL-2 enhancer showed that the GR-responsive elements mapped to regions containing nuclear factor of activated T cells protein (NFAT) (-279 to -263 bp) and AP-1 (-160 to -150 bp) motifs. The AP-1 motif binds TPA and calcium ionophore-induced nuclear factor(s) containing fos protein. TPA and calcium ionophore-induced transcriptional activation of homo-oligomers of the NFAT element were not inhibited by Dex, while AP-1 motif concatemers were not stimulated by TPA and calcium ionophore. When combined, NFAT and AP-1 motifs significantly synergized in directing CAT transcription. Such a synergism was impaired by specific mutations affecting the trans-acting factor binding to either NFAT or AP-1 motifs. In spite of the lack of hormone regulation of isolated cis elements, TPA/calcium ionophore-mediated activation of CAT vectors containing a combination of the NFAT and the AP-1 motifs became suppressible by Dex. Our results show that the IL-2-AP-1 motif confers GR sensitivity to a flanking region containing a NFAT element and suggest that synergistic cooperativity between the NFAT and AP-1 sites allows GR to mediate the Dex inhibition of IL-2 gene transcription. Therefore, a Dex-modulated second level of IL-2 enhancer regulation, based on a combinatorial modular interplay, appears to be present.

Base Sequence↗

PubMed1991

Pleiotropic action of the murine quaking locus: structure of the qkv allele.

The spontaneous allele quakingviable (qkv) exerts effects on myelination and spermiogenesis. The defects generated by qkv were not separated in a multilocus mapping cross that provided a mapping resolution of 0.1 centiMorgans (cM). Furthermore, no distortions suggestive of a large chromosomal anomaly associated with qkv were apparent. One plausible interpretation is that the quaking locus contains more than one functional domain, either organized into overlapping genes or expressed by alternative splicing mechanisms. The cloning needed to analyze this locus will be enhanced by the very high resolution of the meiotic mapping cross reported here. The recombinational distances on this qkv map were compressed compared with those previously reported in a high-resolution map for qkl-1, an embryonic lethal allele of quaking induced by ethylnitrosourea. Additional crosses confirmed prior reports that the sex and the genetic background of the heterozygous parent can affect recombinational distances. These joint effects on recombination are strong enough to account for the discrepancy between the two maps. This variability of two-factor map values leads to the preferred multilocus map-building protocol discussed in the accompanying paper.

Animals↗