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Results for “Expression quantitative trait locus analysis”

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PubMed2004

Genetic dissection of embryo sac fertility, pollen fertility, and their contributions to spikelet fertility of intersubspecific hybrids in rice.

The partial sterility of hybrids has been a major barrier for utilization of the strong heterosis expressed in hybrids between Oryza sativa ssp. indica and O. sativa ssp. japonica. Wide-compatibility varieties, comprising a special class of germplasm, are able to produce fertile hybrids when crossed to both indica and japonica varieties. However, all the work on wide compatibility and majority of studies on indica/japonica hybrid sterility reported so far were based only on spikelet fertility; thus, it is not known to what extent male and female gamete abortions influence hybrid sterility. In this study, we investigated pollen fertility, embryo sac fertility, and spikelet fertility in an F1 population of 202 true hybrid plants derived from a three-way cross ('02428'/'Nanjing 11'//'Balilla'). A partial regression analysis showed that the pollen and embryo sac fertility contributed almost equally to spikelet fertility. QTL analysis based on a linkage map of 191 polymorphic marker loci identified two QTLs for pollen fertility, one QTL for embryo sac fertility, and three QTLs for spikelet fertility. The S5 locus, previously identified as a locus for wide compatibility by spikelet fertility analysis, is a major locus for embryo sac fertility, and a QTL on chromosome 5 had a major effect on pollen fertility. These two loci coincided with the two major QTLs for spikelet fertility. The study also detected a QTL on chromosome 8, showing a large effect on spikelet fertility but no effect on either pollen or embryo sac fertility. Very little interaction among the QTLs was detected. The implications of the findings in rice breeding programs are discussed.

Chromosome Mapping↗
PubMed2005

DNA variation at the invertase locus invGE/GF is associated with tuber quality traits in populations of potato breeding clones.

Starch and sugar content of potato tubers are quantitative traits, which are models for the candidate gene approach for identifying the molecular basis of quantitative trait loci (QTL) in noninbred plants. Starch and sugar content are also important for the quality of processed products such as potato chips and French fries. A high content of the reducing sugars glucose and fructose results in inferior chip quality. Tuber starch content affects nutritional quality. Functional and genetic models suggest that genes encoding invertases control, among other things, tuber sugar content. The invGE/GF locus on potato chromosome IX consists of duplicated invertase genes invGE and invGF and colocalizes with cold-sweetening QTL Sug9. DNA variation at invGE/GF was analyzed in 188 tetraploid potato cultivars, which have been assessed for chip quality and tuber starch content. Two closely correlated invertase alleles, invGE-f and invGF-d, were associated with better chip quality in three breeding populations. Allele invGF-b was associated with lower tuber starch content. The potato invertase gene invGE is orthologous to the tomato invertase gene Lin5, which is causal for the fruit-sugar-yield QTL Brix9-2-5, suggesting that natural variation of sugar yield in tomato fruits and sugar content of potato tubers is controlled by functional variants of orthologous invertase genes.

Alleles↗
PubMed1999

Molecular basis of congenital lp(a) deficiency: a frequent apo(a) 'null' mutation in caucasians.

High plasma concentrations of lipoprotein(a) [Lp(a)], a covalent low-density lipoprotein-apolipoprotein(a) [apo(a)] complex, are associated with coronary heart disease and stroke. Heritability of Lp(a) levels is high and the major locus determining Lp(a) concentrations is the apo(a) gene. We here demonstrate that a G-->A substitution at the +1 donor splice site of the apo(a) kringle (K) IV type 8 intron occurs with a high frequency ( approximately 6%) in Caucasians but not in Africans and is associated with congenital deficiency of Lp(a) in plasma. This mutation alone accounts for a quarter of all 'null' apo(a) alleles in Caucasians. RT-PCR analysis based on apo(a) illegitimate transcription in lympho- blastoid cells demonstrated that the donor splice site mutation results in an alternative splicing of the K IV type 8 intron and encodes a truncated form of apo(a). Expression of the alternatively spliced cDNA analogue in HepG2 cells showed that the truncated apo(a) form is secreted but is unable to form the covalent Lp(a) complex. Immunoprecipitated plasma apo(a) from homozygotes for the mutation was almost completely fragmented. Taken together, our data indicate that a failure in complex formation followed by fast degradation in plasma of the truncated free apo(a) is one mechanism which underlies the null Lp(a) type associated with the donor splice site mutation.

Alleles↗
PubMed2005

Polycomb mediates Myc autorepression and its transcriptional control of many loci in Drosophila.

Aberrant accumulation of the Myc oncoprotein propels proliferation and induces carcinogenesis. In normal cells, however, an abundance of Myc protein represses transcription at the c-myc locus. Cancer cells often lose this autorepression. We examined the control of myc in Drosophila and show here that the Drosophila ortholog, dmyc, also undergoes autorepression. We find that the developmental repressor Polycomb (Pc) is required for dmyc autorepression, and that this Pc-dMyc-mediated repression spreads across an 875-kb region encompassing the dmyc gene. To further investigate the relationship between Myc and Polycomb, we used microarrays to identify genes regulated by each, and identify a striking relationship between the two: A large set of dMyc activation targets is normally repressed by Pc, and 73% of dMyc repression targets require Pc for this repression. Chromatin immunoprecipitation confirmed that many dMyc-Pc-repressed loci have an epigenetic mark recognized by Pc. Our results suggest a novel relationship between Myc and Polycomb, wherein Myc enhances Polycomb repression in order to repress targets, and Myc suppresses Polycomb repression in order to activate targets.

Animals↗
PubMed2006

Fine mapping of the qCTS12 locus, a major QTL for seedling cold tolerance in rice.

The temperate japonica rice cultivar M202 is the predominant variety grown in California due to its tolerance to low temperature stress, good grain quality and high yield. Earlier analysis of a recombinant inbred line mapping population derived from a cross between M202 and IR50, an indica cultivar that is highly sensitive to cold stress, resulted in the identification of a number of QTL conferring tolerance to cold-induced wilting and necrosis. A major QTL, qCTS12, located on the short arm of chromosome 12, contributes over 40% of the phenotypic variance. To identify the gene(s) underlying qCTS12, we have undertaken the fine mapping of this locus. Saturating the short arm of chromosome 12 with microsatellite markers revealed that qCTS12 is closest to RM7003. Using RM5746 and RM3103, which are immediately outside of RM7003, we screened 1,954 F(5)-F(10) lines to find recombinants in the qCTS12 region. Additional microsatellite markers were identified from publicly available genomic sequence and used to fine map qCTS12 to a region of approximately 87 kb located on the BAC clone OSJNBb0071I17. This region contains ten open reading frames (ORFs) consisting of five hypothetical and expressed proteins of unknown function, a transposon protein, a putative NBS-LRR disease resistance protein, two zeta class glutathione S-transferases (OsGSTZ1 and OsGSTZ2), and a DAHP synthetase. Further fine mapping with markers developed from the ORFs delimited the QTL to a region of about 55 kb. The most likely candidates for the gene(s) underlying qCTS12 are OsGSTZ1 and OsGSTZ2.

Chromosome Mapping↗
PubMed2006

Molecular characterization of the equine collagen, type IX, alpha 2 (COL9A2) gene on horse chromosome 2p16-->p15.

The mammalian collagen, type IX, alpha 2 gene (COL9A2) encodes the alpha-2 chain of type IX collagen and is located on horse chromosome 2p16-->p14 harbouring a quantitative trait locus for osteochondrosis. We isolated a bacterial artificial chromosome (BAC) clone containing the equine COL9A2 gene and determined the complete genomic sequence of this gene. Cloning and characterization of equine COL9A2 revealed that the equine gene consists of 32 exons spanning approximately 15 kb. The COL9A2 transcript encodes a single protein of 688 amino acids. Thirty two single nucleotide polymorphisms (SNPs) equally distributed in the gene were detected in a mutation scan of eight unrelated Hanoverian warmblood stallions, including one SNP that affects the amino acid sequence of COL9A2. Comparative analyses between horse, human, mouse and rat indicate that the chromosomal location of equine COL9A2 is in agreement with known chromosomal synteny relationships. The comparison of the gene structure and transcript revealed a high degree of conservation towards the other mammalian COL9A2 genes. We chose three informative SNPs for association and linkage disequilibrium tests in three to five paternal half-sib families of Hanoverian warmblood horses consisting of 44 to 75 genotyped animals. The test statistics did not reach the significance threshold of 5% and so we could not show an association of COL9A2 with equine osteochondrosis.

Amino Acid Sequence↗
PubMed2003

Decreased ethanol preference and wheel running in Nurr1-deficient mice.

Nurr1 (Nr4a2) is a transcription factor expressed in dopamine cells from early development and throughout life. Null mutants for Nurr1 lack the ventral midbrain dopamine neurons and die soon after birth. Animals with a heterozygous deletion are viable and display no apparent abnormality. We have investigated the impact of heterozygous deletion of Nurr1 on ethanol consumption in adult mice as a model for drug-induced reward and on wheel running as a model for natural reward. Interestingly, Nurr1 heterozygous mice never developed high ethanol consumption nor did they develop as much running behaviour as did the wild-type animals. Thus, Nurr1 appears to have a key role for the reinforcing properties of ethanol and running that underlies the development of excessive reward-seeking behaviours characteristic for addiction. Quantitative trait loci mapping using C57Bl/6 and DBA/2 mice describe a locus for ethanol preference on chromosome 2, wherein Nurr1 is located. We found two dinucleotide repeats in the Nurr1 promoter that were longer in mice with low preference for ethanol (DBA/2 and 129/Sv) than in mice with high preference for ethanol (C57Bl/6J and C57Bl/6NIH). These sequential data are compatible with Nurr1 as a candidate gene responsible for the quantitative trait loci for ethanol preference on mouse chromosome 2. Together, our data thus imply involvement of Nurr1 in the transition to a state of high ethanol consumption as well as in the development of a high amount of wheel running in mice.

Alcohol Drinking↗
PubMed2002

Genetic and physiological analysis of germination efficiency in maize in relation to nitrogen metabolism reveals the importance of cytosolic glutamine synthetase.

We have developed an approach combining physiology and quantitative genetics to enhance our understanding of nitrogen (N) metabolism during kernel germination. The physiological study highlighted the central role of glutamine (Gln) synthetase (GS) and Gln synthesis during this developmental process because a concomitant increase of both the enzyme activity and the amino acid content was observed. This result suggests that Gln is acting either as a sink for ammonium released during both storage protein degradation and amino acid deamination or as a source for amino acid de novo synthesis by transamination. In the two parental lines used for the quantitative genetics approach, we found that the increase in Gln occurred earlier in Io compared with F(2), a result consistent with its faster germinating capacity. The genetic study was carried out on 140 F6 recombinant inbred lines derived from the cross between F(2) and Io. Quantitative trait locus mapping identified three quantitative trait loci (QTLs) related to germination trait (T50, time at which 50% of the kernels germinated) that explain 18.2% of the phenotypic variance; three QTLs related to a trait linked to germination performance, kernel size/weight (thousand kernels weight), that explain 17% of the phenotypic variance; two QTLs related to GS activity at early stages of germination that explain 17.7% of the phenotypic variance; and one QTL related to GS activity at late stages of germination that explains 7.3% of the phenotypic variance. Coincidences of QTL for germination efficiency and its components with genes encoding cytosolic GS (GS1) and the corresponding enzyme activity were detected, confirming the important role of the enzyme during the germination process. A triple colocalization on chromosome 4 between gln3 (a structural gene encoding GS1) and a QTL for GS activity and T50 was found; whereas on chromosome 5, a QTL for GS activity and thousand kernels weight colocalized with gln4, another structural gene encoding GS1. This observation suggests that for each gene, the corresponding enzyme activity is of major importance for germination efficiency either through the size of the grain or through its faster germinating capacity. Consistent with the possible nonoverlapping function of the two GS1 genes, we found that in the parental line Io, the expression of Gln3 was transiently enhanced during the first hours of germination, whereas that of gln4 was constitutive.

Chromosome Mapping↗
PubMed2005

Arrested natural killer cell development associated with transgene insertion into the Atf2 locus.

Natural killer (NK) cell development in the bone marrow is not fully understood. Following lineage commitment, these cells appear to advance through a series of developmental stages that are beginning to be characterized. We previously reported a selective deficiency of NK cells in a C57BL/6 mouse with a transgenic construct consisting of the cDNA for the Ly49A major histocompatibility complex (MHC) class 1-specific inhibitory receptor driven by the granzyme A gene. This mouse has few NK cells in peripheral tissues with relative preservation of other immune cells, including T and B cells. Herein we demonstrate that these mice have an accumulation of NK cells with an immature phenotype in the bone marrow, consistent with a block at a previously proposed stage in normal NK-cell development. The phenotype is associated with transgenic insertion into Atf2, the gene for the basic leucine zipper (bZIP) transcription factor family member ATF-2. Although analysis of Atf2-null NK cells shows no defect, the transgenic mice express abnormal truncated Atf2 transcripts that may mediate a repressor effect because ATF2 can heterodimerize with other bZIP molecules. The defect is cell intrinsic, suggesting that certain bZIP molecules play significant roles in NK-cell development.

Activating Transcription Factor 2↗
PubMed1995

Ten allelic apolipoprotein[a] 5' flanking fragments exhibit comparable promoter activities in HepG2 cells.

Plasma levels of the atherogenic lipoprotein[a] represent a quantitative genetic trait that is primarily controlled by the polymorphic apolipoprotein[a] locus on chromosome 6q. The more than 1000-fold variation in lipoprotein[a] plasma levels is explained to a large extent by a remarkable size polymorphism of the apolipoprotein[a] gene which is translated into apolipoprotein[a] isoforms and by unidentified sequence variation in apo[a]. In a recent report, sequence variation in a 1.5 kb fragment from the 5' flanking region of the apolipoprotein[a] gene was associated with different promoter activities, which led to the suggestion that transcriptional control of the apolipoprotein[a] gene might contribute significantly to lipoprotein[a] plasma levels. We have used a reporter gene assay to compare the promoter activities of these 1.5 kb fragments which were cloned from ten well-characterized apolipoprotein[a] alleles. These ten allelic apolipoprotein[a] fragments revealed, despite the same sequence variation as previously reported, comparable and relatively weak promoter activities in HepG2 hepatocarcinoma cells. Promoter activity for the same fragment in non-liver cells and the identification of a liver cell-specific DNaseI hypersensitive site 3 kb upstream from the ATG start codon suggest that longer fragments must be used in order to analyze the transcriptional regulation of the apolipoprotein[a] gene.

Alleles↗
PubMed2025

Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes. METHODS: We performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans-Omics for Precision Medicine reference panel. Fine-mapping and expression quantitative trait locus colocalization analyses in myositis-relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities. RESULTS: Our analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti-histidyl-transfer RNA synthetase autoantibodies (anti-Jo-1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein-Barr virus (EBV)-transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation. CONCLUSION: Our study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.

Humans↗
PubMed2005

Genetic and molecular analyses of natural variation indicate CBF2 as a candidate gene for underlying a freezing tolerance quantitative trait locus in Arabidopsis.

Natural variation for freezing tolerance is a major component of adaptation and geographic distribution of plant species. However, little is known about the genes and molecular mechanisms that determine its naturally occurring diversity. We have analyzed the intraspecific freezing tolerance variation existent between two geographically distant accessions of Arabidopsis (Arabidopsis thaliana), Cape Verde Islands (Cvi) and Landsberg erecta (Ler). They differed in their freezing tolerance before and after cold acclimation, as well as in the cold acclimation response in relation to photoperiod conditions. Using a quantitative genetic approach, we found that freezing tolerance differences after cold acclimation were determined by seven quantitative trait loci (QTL), named FREEZING TOLERANCE QTL 1 (FTQ1) to FTQ7. FTQ4 was the QTL with the largest effect detected in two photoperiod conditions, while five other FTQ loci behaved as photoperiod dependent. FTQ4 colocated with the tandem repeated genes C-REPEAT BINDING FACTOR 1 (CBF1), CBF2, and CBF3, which encode transcriptional activators involved in the cold acclimation response. The low freezing tolerance of FTQ4-Cvi alleles was associated with a deletion of the promoter region of Cvi CBF2, and with low RNA expression of CBF2 and of several CBF target genes. Genetic complementation of FTQ4-Cvi plants with a CBF2-Ler transgene suggests that such CBF2 allelic variation is the cause of CBF2 misexpression and the molecular basis of FTQ4.

Acclimatization↗
PubMed2005

Genomic analysis of the Microphthalmia locus and identification of the MITF-J/Mitf-J isoform.

The deafness-pigmentary disorder Waardenburg Syndrome Type 2 is caused by mutations in the human Microphthalmia-associated transcription factor (MITF) gene. Multiple related deafness-pigmentary disorders result from mutations in genes that regulate MITF expression or its activity. Similarly in mouse, homozygous mutations in the Mitf gene disrupt the development of melanocytes as well as retinal pigment epithelial (RPE) cells, osteoclasts, mast cells, and NK cells. Because abnormalities in Mitf/MITF function are associated with numerous inherited disorders of mouse and man, a detailed understanding of its gene structure is important for both diagnostic and structure/function analyses. While at least eight distinct isoforms of MITF/Mitf have been identified to date, each differing in their promoter and initial exon usage, the positions of these exons and their order within the locus have yet to be fully defined. In this study, we provide a detailed description of the MITF/Mitf locus, identify corresponding human and mouse isoforms, and utilize an informatics-based approach to identify a novel ninth MITF/Mitf isoform, MITF-J/Mitf-J, which we show is expressed in multiple cell types. The MITF/Mitf locus is over 200 kb in length, with strong but imperfect exon conservation between human and mouse. MITF/Mitf tissue expression data are presented from multiple datasets, including EST expression patterns and isoform-specific RT-PCR. The majority of isoforms were found to be broadly expressed, with the M- and Mc-isoforms being tissue-restricted to melanocytes and mast cells, respectively. Consequently, a detailed characterization of this complex locus may help to identify additional unknown deafness-pigmentary syndrome mutations in human kindred and permit a better understanding of tissue-regulated expression that likely underlies divergent biological functions of this factor across multiple cell types.

Animals↗
PubMed2005

MHC-F DNA sequences in bonobo, gorilla and orangutan.

The major histocompatibility complex (MHC)-F class Ib locus shows a limited polymorphism, and the function of its mainly intracellular protein is not clear. We have identified human leucocyte antigen (HLA)-F orthologous DNA sequences in Pongidae in order to study the MHC-F gene evolution and its products' function. HLA-F orthologous cDNA transcripts are found in chimpanzee and in the new primate species studied (bonobo, gorilla and orangutan). Analyses of the predicted amino acid sequences and their comparison with other primate MHC-F proteins show that MHC-F may be a protein with a typical class I structure and that the key residues of the peptide-binding region (PBR) are highly conserved in MHC-F in all studied primates species. Thus, MHC-F conservation along the primate evolution suggests an important role in cellular physiology. It is possible that the MHC-F protein could be involved, together with MHC-G and MHC-E, in the natural killer (NK) cell activity regulation, although rhesus macaque does not express MHC-G and MHC-E orthologues. The evolutionary pathway of the six-base-pair deletion at exon 2 existing in some primates is put forward.

Amino Acid Sequence↗
PubMed2004

Corticosteroid binding globulin: a new target for cortisol-driven obesity.

We present data suggesting that corticosteroid-binding globulin (CBG) may be the causal gene of a previously identified quantitative trait locus (QTL) associated with cortisol levels, fat, and muscle content in a pig intercross. Because Cbg in human and mouse maps in the region orthologous to the pig region containing this QTL, we considered Cbg as an interesting positional candidate gene because CBG plays a major role in cortisol bioavailability. Firstly, we cloned pig Cbg from a bacterial artificial chromosome library and showed by fluorescent in situ hybridization and radiation hybrid mapping that it maps on 7q26 at the peak of the QTL interval. Secondly, we detected in a subset of the pig intercross progeny a highly significant genetic linkage between CBG plasma binding capacity values and the chromosome 7 markers flanking the cortisol-associated QTL. In this population, CBG capacity is correlated positively to fat and negatively to muscle content. Thirdly, CBG capacity was three times higher in Meishan compared with Large White parental breeds and a 7-fold difference was found in Cbg mRNA expression between the two breeds. Overall, the data accumulated in this study point to Cbg gene as a key regulator of cortisol levels and obesity susceptibility.

Adipose Tissue, Brown↗
PubMed2003

Cosegregation analysis of natriuretic peptide genes and blood pressure in the spontaneously hypertensive rat.

1. The natriuretic peptide precursor A (Nppa) and B (Nppb) genes are candidate genes for hypertension and cardiac hypertrophy in the spontaneously hypertensive rat (SHR). The purpose of the present study was to determine the role of the Nppa and Nppb genes in the development of hypertension in the SHR. 2. A cohort (n = 162) of F2 segregating intercross animals was established between strains of hypertensive SHR and normotensive Wistar-Kyoto rats. Blood pressure and heart weight were measured in each rat at 12-16 weeks of age. Rats were genotyped using 11 informative microsatellite markers, distributed in the vicinity of the Nppa marker on rat chromosome 5 including an Nppb marker. The phenotype values were compared with genotype using the computer package mapmaker 3.0 (Whitehead Institute, Boston, MA, USA) to determine whether there was a link between the genetic variants of the natriuretic peptide family and blood pressure or cardiac hypertrophy. 3. A strong correlation was observed between the Nppa marker and blood pressure. A quantitative trait locus (QTL) for blood pressure on chromosome 5 was identified between the Nppa locus and the D5Mgh15 marker, less than 2 cM from the Nppa locus. The linkage score for the blood pressure QTL on chromosome 5 was 3.8 and the QTL accounted for 43% of the total variance of systolic blood pressure, 54% of diastolic blood pressure and 59% of mean blood pressure. No association was found between the Nppb gene and blood pressure. This is the first report of linkage between the Nppa marker and blood pressure in the rat. There was no correlation between the Nppa or Nppb genes or other markers in this region and either heart weight or left ventricular weight in F2 rats. 4. These findings suggest the existence of a blood pressure-dependent Nppa marker variant or a gene close to Nppa predisposing to spontaneous hypertension in the rat. It provides a strong foundation for further detailed genetic studies in congenic strains, which may help to narrow down the location of this gene and lead to positional cloning.

Animals↗
PubMed2003

Molecular characterization and expression of porcine bone morphogenetic protein receptor-IB in the uterus of cyclic and pregnant gilts.

Previous gene mapping analyses revealed a quantitative trait locus for uterine capacity on chromosome 8. Comparison of porcine and human genetic maps suggests that the bone morphogenetic protein receptor IB (BMPR-IB) gene may be located near this region. The objectives of this study were to 1) clone the full coding region for BMPR-IB, 2) examine BMPR-IB gene expression by the endometrium and its cellular localization in cyclic and pregnant gilts, and 3) map the BMPR-IB gene. By iterative screening of an expressed sequence tag library, we obtained a 3559-base pair cDNA clone including the full coding region of BMPR-IB. Endometrial BMPR-IB mRNA expression of White composite gilts was determined by Northern blotting in Days 10, 13, and 15 cyclic and Days 10, 13, 15, 20, 30, and 40 pregnant gilts. In cyclic gilts, endometrial BMPR-IB mRNA expression was elevated on Days 13 and 15 (P < 0.01) compared with Day 10. Expression of BMPR-IB mRNA was localized in both luminal and glandular epithelium on Day 15. However, in pregnant gilts, BMPR-IB mRNA expression was not significantly different in the endometrium from Day 10 to Day 20, and it was significantly decreased on Days 30 and 40 (P = 0.011). The BMPR-IB gene was mapped to 108 cM on chromosome 8. These findings show that BMPR-IB mRNA expression is regulated differently in cyclic and pregnant gilts; this pattern of gene expression may be important for endometrial function during the luteal phase of the estrous cycle as compared with early pregnancy.

Amino Acid Sequence↗
PubMed2004

The zebrafish iguana locus encodes Dzip1, a novel zinc-finger protein required for proper regulation of Hedgehog signaling.

Members of the Hedgehog (Hh) family of intercellular signaling molecules play crucial roles in animal development. Aberrant regulation of Hh signaling in humans causes developmental defects, and leads to various genetic disorders and cancers. We have characterized a novel regulator of Hh signaling through the analysis of the zebrafish midline mutant iguana (igu). Mutations in igu lead to reduced expression of Hh target genes in the ventral neural tube, similar to the phenotype seen in zebrafish mutants known to affect Hh signaling. Contradictory at first sight, igu mutations lead to expanded Hh target gene expression in somites. Genetic and pharmacological analyses revealed that the expression of Hh target genes in igu mutants requires Gli activator function but does not depend on Smoothened function. Our results show that the ability of Gli proteins to activate Hh target gene expression in response to Hh signals is generally reduced in igu mutants both in the neural tube and in somites. Although this reduced Hh signaling activity leads to a loss of Hh target gene expression in the neural tube, the same low levels of Hh signaling appear to be sufficient to activate Hh target genes throughout somites because of different threshold responses to Hh signals. We also show that Hh target gene expression in igu mutants is resistant to increased protein kinase A activity that normally represses Hh signaling. Together, our data indicate that igu mutations impair both the full activation of Gli proteins in response to Hh signals, and the negative regulation of Hh signaling in tissues more distant from the source of Hh. Positional cloning revealed that the igu locus encodes Dzip1, a novel intracellular protein that contains a single zinc-finger protein-protein interaction domain. Overexpression of Igu/Dzip1 proteins suggested that Igu/Dzip1 functions in a permissive way in the Hh signaling pathway. Taken together, our studies show that Igu/Dzip1 functions as a permissive factor that is required for the proper regulation of Hh target genes in response to Hh signals.

Amino Acid Sequence↗