SEARCH · PubMed Health

Results for “Single locus”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources

PubMed2002

A sex-linked locus controls wing polymorphism in males of the pea aphid, Acyrthosiphon pisum (Harris).

Discrete variation in wing morphology is a very common phenomenon in insects and has been used extensively in the past 50 years as a model to study the ecology and evolution of dispersal. Wing morph determination can be purely genetic, purely environmental, or some combination of the two. The precise genetic determinants of genetically based wing morph variation are unknown. Here we explore the genetic basis of wing polymorphism in the pea aphid, which can produce either winged or wingless males. We confirm that three types of pea aphid clones coexist in natural populations, those producing winged males only, those producing wingless males only, and those producing a mixture of both. A Mendelian genetic analysis reveals that male wing polymorphism in pea aphids is determined by a single locus, two alleles system. Using microsatellite loci of known location, we show that this locus is on the X chromosome. The existence of a simple genetic determinism for wing polymorphism in a system in which genetic investigation is possible may help investigations on the physiological and molecular mechanisms of genetically-based wing morph variation. This locus could also be used in the search for genes involved in the wing polyphenism described in parthenogenetic females and to investigate the interplay between polymorphisms and polyphenisms.

Alleles↗

PubMed2005

A deletion causing spontaneous fracture identified from a candidate region of mouse Chromosome 14.

Map-based cloning is an iterative approach that identifies the underlying genetic cause of a mutant phenotype. However, the classic protocol of positional cloning is time-consuming and labor-intensive. We now describe a genome sequence-based cloning approach that has led to localizing the underlying genetic cause of spontaneous fractures (sfx) in a mouse model. The sfx/sfx mouse is characterized by a spontaneous femoral fracture seen around 6 weeks of age, which represents a new mouse model for bone fragility. Genetic studies indicate that the phenotype of sfx/sfx mice is caused by an alteration at a single locus that is roughly mapped onto the central region of mouse Chromosome 14. Using our strategy of combining mouse genome resources and high-throughput technology, we discovered a deletion of all 12 exons in the gene for L-gulonolactone oxidase (LGO), a key enzyme in the synthesis of ascorbic acid. We have also examined the expression of LGO and found no expression of LGO in sfx mice while the LGO expresses in several tissues of normal mice. Our data demonstrated the feasibility to positionally clone the mutated gene from a non-fine-mapped locus, which has applicability to the positional cloning of genes from many other animal models, as their genome sequences are sequenced or will be sequenced soon.

Animals↗

PubMed2006

Brain-derived neurotrophic factor and risk of schizophrenia: an association study and meta-analysis.

Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as neural survival, differentiation, and plasticity. Previous studies have suggested that variants in the BDNF gene increase the risk of schizophrenia. In this study, we genotyped one (GT)n dinucleotide repeat and three SNPs (rs6265, rs2030324, and rs2883187) in a Chinese sample (617 cases and 672 controls). In addition, we performed an updated meta-analysis based on 16 population-based case-control studies examining association between rs6265 and schizophrenia. In single-locus analysis, no significant association was found between BDNF polymorphisms and schizophrenia in our subjects. The meta-analysis based on Asian and Caucasian subjects did not give positive result that rs6265 is associated with schizophrenia. However, haplotype analysis found a common four-locus haplotype is protective against schizophrenia (Case 3.1% vs Control 7%, p=0.0011). Our data provides evidence that BDNF is a susceptibility gene for schizophrenia in Chinese subjects.

Adult↗

PubMed1981

Genetic studies of the murine corneal response to Pseudomonas aeruginosa.

The murine genetic control of resistance to Pseudomonas aeruginosa eye infection previously has been demonstrated to be regulated by two complementing dominant genes, PsCR1 and PsCR2. The PsCR1 locus apparently is not associated with the H-2 complex, whereas the PsCR2 locus could not definitively be associated with H-2. In this study we attempted to demonstrate a possible H-2 linkage of the PsCR2 locus. A panel of inbred congenic strains varying with either the H-2 haplotype or genetic background from inbred partners of C57BL/10, C3H, A, and BALB/c strains were characterized for their P. aeruginosa infectivity phenotypes. These studies indicated that the PsCR2 locus is not associated with the H-2 locus. Furthermore, variations of the H-2 haplotype did not change the resistance patterns observed in these strains. However, BALB.B and BALB.K congenic lines were resistant to P. aeruginosa eye infection, whereas BALB/cJ mice were susceptible. Examination of hybrids (BALB.K X BALB/cJ)F1 and (BALB.B X BALB/cJ)F1 demonstrated that an autosomal dominant gene(s), PsCR, confers resistance. Segregation analysis for the H-2 haplotype and the PsCR gene in offspring of backcross matings with the BALB/cJ parental strain suggested that this PsCR gene is not linked to the H-2 complex and has an inheritance pattern of a single locus or several tightly linked loci.

Animals↗

PubMed2001

Diverse virulence traits underlying different clinical outcomes of Salmonella infection.

Salmonella strains have evolved to infect a wide variety of reptiles, birds, and mammals resulting in many different syndromes ranging from colonization and chronic carriage to acute fatal disease. Adaptation to a large number of different evolutionary niches has undoubtedly driven the high degree of phenotypic and genotypic diversity in Salmonella strains. Differences in LPS and flagellar structure generate the antigenic variation that is reflected in the more than 2,000 known serotypes. Moreover, variations of LPS structure affect the virulence of the strain. The differential expression of various fimbriae by Salmonella is likely to be due to the wide variety of mucosal surfaces that are encountered by various strains, and the host immune response may select for a different expression pattern. As with these surface structures, a variety of other important virulence determinants show a variable distribution in Salmonella strains and also serve to delineate the divergence of the Salmonella lineage from E. coli. The acquisition of the SPI-1 region may have represented the defining genetic event in the separation of the Salmonella and E. coli lineages. The SPI-1 cell invasion function allowed Salmonella to establish a separate niche in epithelial cells. The mgtC locus on SPI-3 is also present in all lineages and facilitates the adaptation of the bacteria to the low Mg2+, low pH environment of the endosome that results from SPI-1-mediated invasion. Subsequent acquisition of SPI-2 allowed Salmonella to manipulate the sorting of the endosome or phagosome, altering the intracellular environment and facilitating bacterial growth within infected cells. The ability to disseminate from the bowel and establish extraintestinal niches is promoted by the spv locus. Since Salmonella proliferates within macrophages and must avoid phagocytosis by neutrophils to establish a systemic infection, the spv genes appear to promote the macrophage phase of the disease process. Here the polymorphism of the spv locus is clearly demonstrated, since the serovars that cause most cases of nontyphoid bacteremia contain the spv genes. The absence of the spv genes from S. typhi is particularly puzzling and is a strong indication that the pathogenesis of typhoid fever is fundamentally different from that of bacteremia due to nontyphoid Salmonella. There is currently no genetic explanation for the phenotype of host adaptation or for the finding that only a few serovars cause the majority of human infections. Based on recent findings that multiple individual virulence genes have a variable distribution in Salmonella, it is unlikely that a single locus will be found to be responsible for these complex biological traits. Instead, a complicated combination of genes are likely to contribute to the overall virulence phenotype.

Animals↗

PubMed2006

The Sbm1 locus conferring resistance to Soil-borne cereal mosaic virus maps to a gene-rich region on 5DL in wheat.

A mosaic disease caused by Soil-borne cereal mosaic virus (SBCMV) is becoming increasingly important, particularly in winter wheat in Europe. As there are currently no effective cultural practices or practical environmentally friendly chemicals for disease control, host plant resistance is an important objective in breeding programs. However, development of resistant cultivars is slow owing to difficulties in germplasm screening for resistance. Therefore, there is a need to identify molecular markers linked to SBCMV-resistance gene(s), so that quick and accurate laboratory-based marker-assisted selection rather than prolonged field-based screens for resistance can be used in developing resistant cultivars. We previously demonstrated that resistance to SBCMV in Triticum aestivum 'Cadenza' is controlled by a single locus. In this work, we used AFLP and microsatellite technology to map this resistance locus, with the proposed name Sbm1, to the distal end of chromosome 5DL. Interestingly, several expressed disease-resistance gene analogues also map to this gene-rich region on 5DL. Closely linked (approximately 17 cM interval) markers, BARC110 and WMC765, RRES01 and BARC144, that flank Sbm1 will be very useful in breeding for selection of germplasm carrying Sbm1.

Base Sequence↗

PubMed1991

Genetic mapping of the chloroquine-resistance locus on Plasmodium falciparum chromosome 7.

The resurgence of malaria in recent decades has been accompanied by the worldwide spread of resistance to chloroquine, a drug once uncontested as the first-line antimalarial agent because of its efficacy and low toxicity. Chloroquine-resistant strains of Plasmodium falciparum counter the drug by expelling it rapidly via an unknown mechanism. In the absence of explicit biochemical knowledge of this efflux mechanism, reverse genetics provides a powerful approach to the molecular basis of chloroquine resistance. Here we report genetic linkage analysis in which 85 restriction fragment length polymorphism markers were used to examine inheritance of the 14 P. falciparum chromosomes in a laboratory cross between a chloroquine-resistant and a chloroquine-sensitive parasite. Inheritance data from 16 independent recombinant progeny show that the rapid efflux, chloroquine-resistant phenotype is governed by a single locus within an approximately 400-kilobase region of chromosome 7. Identification and characterization of genes within this region should lead to an understanding of the chloroquine-resistance mechanism.

Animals↗

PubMed2005

Population genetics of multi-host parasites--the case for molecular epidemiological studies of Schistosoma japonicum using larval stages from naturally infected hosts.

Population genetics of multi-host pathogens offers great potential for the understanding of their complex epidemiology but care must be taken to ensure that the sampling procedure does not bias estimates of population indices. The transfer of material to laboratory passage, in particular, runs the risk of bottlenecking and imposing non-random host-induced selection pressures according to the hosts used in passage. We present a novel technique allowing single-locus microsatellite genotyping of the naturally sampled larval stages, enabling unbiased population genetic studies of the multi-host zoonotic parasite Schistosoma japonicum. The utility of these larval genotyping methods for molecular epidemiological studies are illustrated in results from 3 separate data sets. In the first data set, potential loss of alleles based on the definitive host species used for laboratory maintenance was identified by comparing adult worm populations derived from mice and rabbits infected with cercarial populations originating from the same set of snails. In the second data set, bottlenecking was demonstrated by the loss of alleles in adult worms derived within a single generation of laboratory maintenance compared to their parent field-collected cercarial samples. In the final data set, comparison of miracidia and adult worms recovered from naturally infected animals demonstrated that larval analyses can provide stage-specific epidemiological information and that population genetics of schistosomes can be well described by analysis of larval stages. Our results thus advocate the use of natural life-cycle stages to obtain an accurate and ethical representation of the population genetic structure of S. japonicum and other multi-host pathogens.

Animals↗

PubMed1982

Physiological studies of canine sympathetic ganglia and cardiac nerves.

Anatomical studies have indicated that the middle cervical ganglion is the primary locus of sympathetic postganglionic neurons which have axons projecting in canine cardiac nerves. Small regions of thoracic sympathetic ganglia were stimulated electrically with bipolar electrodes and the generated compound action potentials were recorded from ipsilateral cardiac nerves. Several procedures were used to distinguish the effects of stimulating preganglionic axons, ganglionic sites and postganglionic axons. Following hexamethonium it was found that only low frequency stimulation (e.g. 1 Hz) of ganglionic sites resulted in the generation of compound action potentials in cardiac nerves. These ganglionic sites were located throughout the middle cervical ganglion, but only in the cranial medial pole of the stellate ganglion. Stimulation of a single locus in a stellate or middle cervical ganglion generated compound action potentials in all major ipsilateral sympathetic cardiac nerves. A ganglion was also identified at the junction of the thoracic vagus and the cranial vagal nerve which may be as important as the right stellate ganglion in cardiac regulation. These results demonstrate that there are discrete loci in thoracic ganglia which contain neurons projecting in several ipsilateral cardiac nerves. Low frequency stimulation of these loci was found to be optimal for generation of compound action potentials.

Animals↗

PubMed1988

Rip locus: regulation of female-specific isozyme (I-P-450(16 alpha) of testosterone 16 alpha-hydroxylase in mouse liver, chromosome localization, and cloning of P-450 cDNA.

The constitutive expression of phenobarbital-inducible mouse cytochrome P-450 (I-P-450(16 alpha) at the mRNA level and its associated testosterone 16 alpha-hydroxylase activity in liver microsomes was a female characteristic in many inbred mice, including BALB/cJ, A/HeJ, and C57BL/6J. This sex-dependent constitutive expression of the mRNA and enzyme activity was severely reduced in females of mouse strain 129/J. The distribution patterns of the mRNA and activity levels in individual offspring of F1, F2, and F1 backcrosses to progenitors, generated from crosses between 129/J and BALB/cJ mice, indicated that the female-specific expression of I-P-450(16 alpha) is an autosomal dominant trait under the regulation of a sex-limited single locus. It was found that the genotypes of this locus exhibited concordance with that of the coumarin hydroxylase locus (Coh locus) in eight out of nine 9 X A recombinant inbred strains, suggesting the localization of this sex-limited locus on chromosome 7. We propose Rip (regulation of sex-dependent, constitutive expression of phenobarbital-inducible P-450) as the name of this sex-limited locus. With the use of the rat P-450e cDNA probe, a cDNA library from liver poly(A+) RNA of BALB/cJ was screened, and three distinct cDNAs (pf3, pf26, and pf46) were selected on the basis of their restriction patterns. Nucleotide sequences of the cDNAs revealed that pf3 and pf46 are clones overlapped, with the exception that the 27-bp DNA is inserted in the coding region of pf46. The nucleotide sequence (named pf3/46) obtained from the overlapping sequences of pf3 and pf46 contained 1473 or 1500 bp of open-reading frame, and the deduced amino acid sequence shared 93% similarity with those of rat P-450b. The 27-bp insertion resulted in nine extra amino acids just in front of the cysteine residue, the fifth ligand for heme binding. The mRNA with 27-bp insertion was ubiquitously present in other inbred mice such as A/HeJ and C57BL/6J, but not in 129/J. S-1 nuclease analysis estimated a ratio of p46 and pf3 to be 1:50. Nucleotide and deduced amino acid sequences of the 1473-bp open-reading frame in pf26 possessed 83% similarity to those of pf3/46. Hybridizations of oligonucleotide probes (pf26-cu and pf3/46-cu) specific to either pf26 or pf3/46 with liver poly(A+) RNA from males and females of BALB/cJ, 129/F, and F1 offspring demonstrated that the expression of pf26, but not pf3/46, mRNA was associated with the autosomal dominant inheritance of I-P-450(16 alpha).(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

PubMed1994

Genes within the HLA class II region confer both predisposition and resistance to primary biliary cirrhosis.

Nonradioactive sequence-specific oligonucleotide probes for the polymorphic HLA class II genes have been used to type samples from 51 Caucasian patients with the autoimmune liver disease, primary biliary cirrhosis, and 240 Caucasian controls. Although the allelic distribution at the DPB1 locus showed no significant variation between patients and controls, there was heterogeneity in the distribution of DR-DQ haplotypes where the frequency of the DRB1*0801-DQA1*0401/0601-DQB1*04 haplotype was significantly increased in the patients, suggesting it confers susceptibility to this disease. Two other haplotypes, DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1302-DQA1*0102-DQB1*0604, were significantly reduced in the patients, suggesting they confer protection. Tests of the individual loci show that resistance to this disease is most strongly associated with the DQA1*0102 allele shared by both protective haplotypes. Due to linkage disequilibrium it is unclear whether multiple genes or a single locus on the susceptible DR8 haplotype are needed for predisposition. These data show that distinct HLA class II alleles confer both predisposition and resistance to PBC and provide insight into the role that these genes may play in the immunopathogenesis of this disease.

Causality↗

PubMed1995

Genetic mapping and non-Mendelian segregation of mating type loci in the oomycete, Phytophthora infestans.

DNA markers linked to the determinants of mating type in the oomycete, Phytophthora infestans, were identified and used to address the genetic basis of heterothallism in the normally diploid fungus. Thirteen loci linked to the A1 and A2 mating types were initially identified by bulked segregant analysis using random amplified polymorphic DNA markers (RAPDs) and subsequently scored in three crosses polymorphisms (SSCP), cleaved amplified polymorphisms (CAPS), or allele-specific polymerase chain reaction markers (AS-PCR). All DNA markers mapped to a single region, consistent with a single locus determining both mating types. Long-range restriction mapping also demonstrated the linkage of the markers to one region and delimited the mating type locus to a 100-kb region. The interval containing the mating type locus displayed non-Mendelian segregation as only two of the four expected genotypes were detected in progeny. This is consistent with a system of balance lethal loci near the mating type locus. A model for mating type determination is presented in which the balanced lethals exclude form progeny those with potentially conflicting combinations of mating type alleles, such as those simultaneously expressing A1 and A2 functions.

Base Sequence↗

PubMed1997

Histocompatibility gene mutation rates in the mouse: a 25-year review.

Mutation rates of H2 and non-H2 histocompatibility genes in the mouse are examined over a 25-year period. Detected by skin graft rejections, the mutations were screened in inbred and hybrid mice from a continuously maintained and monitored colony and from a regularly supplied set of mice provided from the National Cancer Institute for monitoring of genetic integrity. Twenty-five H2 mutations were recovered, involving the K, D, L, and Ab loci, as well as over 80 mutations of non-H2 histocompatibility genes. Aside from a single allele at a single locus (H2-Kb), the spontaneous mutation rate of H2 class I genes appears to be equivalent to that found estimated for non-H2 histocompatibility genes, and comparable to rates reported for a variety of mouse genes. This is in contrast with previous suggestions that H2 genes mutate at orders of magnitude greater than do "average" mammalian genes. The discrepancy is attributed to the H2-Kb gene which accounts for over half of all reported H2 mutations and which mutates spontaneously at a rate of 1-2 x 10(-4) per gene per generation. Furthermore, over half of the spontaneous H2-Kb mutations result in a single mutant phenotype (the "bg" group) which involve similar changes at amino acid residues 116 and 121. Thus, the high spontaneous mutation rate for H2-Kb appears to be the exception among major histocompatibility genes, rather than the rule.

Animals↗

PubMed1995

Localization to chromosome 10 of a locus influencing morphine analgesia in crosses derived from C57BL/6 and DBA/2 strains.

A quantitative trait locus (QTL) was detected and mapped to proximal chromosome 10 near the markers Mpmv5 and D10Mit51 with a strong influence on morphine-induced analgesia in the BXD recombinant inbred (RI) strains and in an F2 cross (B6D2F2) between the BXD progenitor strains, C57BL/6 and DBA/2. A LOD score of 3.9 (p < .00002) was seen for analgesia using the hot plate assay. Naloxone Bmax was also associated with this chromosome region in BXD RI mice. The mu opioid receptor gene (Oprm) has recently been mapped to this same chromosome region. The observation that several morphine-related traits and naloxone Bmax appear to be partly determined by this presumed single locus is consistent with the hypothesis that the mu opioid receptor gene, or one of its modulators, is the basis for the QTL.

Analgesia↗

PubMed2005

Influence of the eNOS gene on development of blood pressure and left ventricular mass: longitudinal findings in multiethnic youth.

OBJECTIVES: To evaluate the impact of the endothelial nitric oxide synthase (eNOS) gene on longitudinal development of blood pressure (BP) and left ventricular mass (LVM) from childhood into early adulthood. METHODS: Three polymorphisms including -922A>G, intron 4VNTR, and Glu298Asp of the eNOS gene were investigated. Individual growth-curve modeling and haplotype trend regression analyses were conducted for 579 white and black American youths with 12 assessments over a 15-year period. RESULTS: Significantly different allele and genotype frequencies were observed between blacks and whites for all three polymorphisms. Linkage disequilibrium (LD) patterns among these polymorphisms were also different between ethnic groups: strong LD between the -922A>G and intron 4 VNTR loci was observed in whites but not in blacks. Single locus analyses identified a significant interaction between the intron 4 VNTR and gender on diastolic BP (DBP) levels. The 4a allele carriers had significantly lower DBP levels in males (P=0.012), but higher DBP levels in females (P=0.045). Haplotype analyses confirmed the DBP lowering effect in males (P=0.049). DBP in males homozygous for haplotype G-4a-Glu was 2.58 mmHg lower than males homozygous for the most common haplotype (A-non4a-Glu). Additionally, individuals homozygous for haplotype G-non4a-Glu showed a 0.51 mmHg steeper increase in DBP per year with age as compared to the most common haplotype (P=0.007). No associations between single polymorphisms or haplotypes of the eNOS gene and systolic BP or LVM were found. CONCLUSIONS: our results suggest that eNOS gene may have gender-specific and age-dependent effects on DBP and the development of hypertension risk.

Age Factors↗

PubMed1969

Linkage and selection: new equilibrium properties of the two-locus symmetric viability model.

In the two-locus symmetric viability model with recombination, conditions for the existence and stability of a new class of polymorphic equilibria are given. These "unsymmetric" equilibria, which exist for relatively loose linkage, can be explicitly obtained, in contrast to the previously known symmetric equilibria which are generally given by the solutions of a cubic equation. For sufficiently tight linkage, there is always at least one stable symmetric equilibrium. Seven is the precise maximum for the number of interior equilibria. The qualitative consequences of these results are briefly examined. In particular it is pointed out that since for some linkage values no stable polymorphic equilibria exist, there is no "overdominance theorem" comparable to the single-locus case.

Genotype↗

PubMed1999

Identification of the gene encoding homoserine kinase from Arabidopsis thaliana and characterization of the recombinant enzyme derived from the gene.

Homoserine kinase (EC 2.7.1.39) catalyzes the formation of O-phospho-l-homoserine, a branch point intermediate in the pathways for Met and Thr in plants. A genomic open reading frame located on the top arm of chromosome II and a corresponding cDNA have been identified from Arabidopsis thaliana that encode homoserine kinase. The HSK gene is composed of an 1113-bp continuous open reading frame that could produce a 38-kDa protein. The gene product has homology with homoserine kinase from bacteria and fungi. It contains a conserved motif, known as GHMP, found in a group of ATP-dependent metabolite kinases and thought to comprise the ATP binding site. The amino-terminal 50 amino acids of the HSK protein show features of a transit peptide for localization to plastids. Genomic blot analysis revealed that there is a single locus in A. thaliana to which the HSK cDNA hybridizes. The HSK protein expressed as a His-tagged construct in Escherichia coli shows a specific activity in an l-homoserine-dependent ADP synthesis assay of 3.09 +/- 0.25 micromol min(-1) mg(-1) protein at pH 8.5 and 37 degrees C. The apparent K(m) values are 0.40 mM for l-homoserine and 0.32 mM for Mg-ATP. Other hydroxylated compounds are not used as substrates. The enzyme requires 40 mM K(+) and 3 mM Mg(2+) for activity. It has an unusually high temperature optimum, yet it is very unstable, losing more than 80% of its activity after a single cycle of freeze-thawing. The HSK enzyme shows no significant regulation by amino acids in vitro.

Amino Acid Sequence↗

PubMed1997

Unravelling a complex trait: the genetics of insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM), also known as type 1 or juvenile diabetes, is one of the first disorders with a complex genetic basis that researchers have begun to unravel. More than 20 years ago, the HLA region was found to contain a major locus that influences predisposition to IDDM, and a decade ago a locus with a smaller effect was identified in the insulin-gene region. With the advent of numerous microsatellite markers suitable for genome screening, an additional 6 loci that influence susceptibility to IDDM have been reported since late 1994. This paper summarizes that progress, with particular emphasis on research conducted by Field and associates. Some of the new loci appear to predispose people to IDDM independently of HLA and may be important factors in families with IDDM who lack strong HLA susceptibility. Other loci may interact to cause susceptibility, and specific combinations may be especially diabetogenic. Although isolating the actual predisposing genes in IDDM is more difficult than isolating those involved in single-locus genetic disorders, the fact that the genes can be identified with the use of a reasonable number of families is very encouraging for future research on other genetically complex disorders.

Diabetes Mellitus, Type 1↗