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At least 127 records · Page 7Linked to original sources
PubMed1989

Human pepsinogen C (progastricsin) polymorphism: evidence for a single locus located at 6p21.1-pter.

A series of six clones containing the entire human pepsinogen C gene (PGC) was identified in a cosmid vector library by using cDNA and oligonucleotide probes. The 10.7-kb PGC gene includes nine exons and exhibits a high degree of sequence identity (60%) with the functionally related pepsinogen A genes. The predicted amino acid sequence was identical with the partial amino-terminal and carboxyl-terminal sequences of purified pepsinogen C. An informative restriction fragment length polymorphism was detected with several restriction enzymes and involved an insertion or deletion of 100 bp of intron sequence located between exons 7 and 8. Evidence that there is only a single PGC gene in humans is presented. The PGC gene and the prolactin gene were regionally localized to 6p21.1-pter by analysis of mouse X human somatic cell hybrids.

Amino Acid Sequence↗
PubMed1973

Inherited biochemical variation in Drosophila melanogaster: noise or signal? I. Single-locus analysis.

A study was conducted using small effective population size as an experimental design to test selective neutrality of seven isozyme polymorphisms. Loci varied as to the degree to which the decay of heterozygosity over 21 generations was retarded. Selection for heterozygotes, overdominance, is implicated for at least four of seven loci. Of these ADH gave the largest heterozygote excess in the presence of inbreeding. An interaction between the small population size treatment and excess heterozygosity suggests that (1) the loci studied may be selectively neutral and linked to other loci which are under the influence of selection or (2) the selection coefficients for the loci studied are not independent of the background genotype. In either case four of the seven enzymes studied are signaling the operation of selection. The problem of distinguishing the effect of a single marker from that of a chromosome segment is emphasized. The identification of the genetic unit of selection is crucial to any interpretation of the meaning of enzyme polymorphisms.

Alcohol Oxidoreductases↗
PubMed1995

Ca2+ channel selectivity at a single locus for high-affinity Ca2+ interactions.

Ca2+ channels display remarkable selectivity and permeability, traditionally attributed to multiple, discrete Ca2+ binding sites lining the pore. Each of the four pore-forming segments of Ca2+ channel alpha 1 subunits contains a glutamate residue that contributes to high-affinity Ca2+ interactions. Replacement of all four P-region glutamates with glutamine or alanine abolished micromolar Ca2+ block of monovalent current without revealing any additional independent high-affinity Ca2+ binding site. Pairwise replacements of the four glutamates excluded the hypothesis that they form two independent high-affinity sites. Systematic alterations of side-chain length, charge, and polarity by glutamate replacement with aspartate, glutamine, or alanine weakened the Ca2+ interaction, with considerable asymmetry from one repeat to another. The P-region glutamate in repeat I was unusual in its sensitivity to aspartate replacement but not glutamine substitution. While all four glutamates cooperate in supporting high-affinity interactions with single Ca2+ ions, they also influence the interaction between multiple divalent cations.

Alanine↗
PubMed2002

Pheromone binding proteins of Epiphyas postvittana (Lepidoptera: Tortricidae) are encoded at a single locus.

The light brown apple moth, Epiphyas postvittana (Tortricidae: Lepidoptera) uses a blend of (E)-11-tetradecenyl acetate and (E,E)-9,11-tetradecadienyl acetate as its sex pheromone. Odorant binding proteins, abundant in the antennae of male and female E. postvittana, were separated by native PAGE to reveal four major proteins with distinct mobilities. Microsequencing of their N-terminal residues showed that two were general odorant binding proteins (GOBPs) while two were pheromone binding proteins (PBPs). Full length cDNAs encoding these proteins were amplified using a combination of PCR and RACE-PCR. Sequence of the GOBPs revealed two genes (EposGOBP1, EposGOBP2), similar to orthologues in other species of Lepidoptera. Eleven cDNAs of the PBP gene were amplified, cloned and sequenced revealing two major phylogenetic clusters of PBP sequences differing by six amino acid substitutions. The position of the six amino acid differences on the protein was predicted by mapping onto the three-dimensional structure of PBP of Bombyx mori. All six substitutions were predicted to fall on the outside of the protein away from the inner pheromone binding pocket. One substitution does fall close to the putative dimerisation region of the protein (Ser63Thr). Expression of three of the cDNAs in a baculovirus expression system revealed that one class encodes an electrophoretically slow form (EposPBP1-12) while the other encodes a fast form (EposPBP1-2, EposPBP1-3). A native Western of these expressed proteins compared with antennal protein extracts demonstrated that PBP is also expressed in female antennae and that PBP may be present as a dimer as well as a monomer in E. postvittana. The fast and slow forms of EposPBP1 are allelic. Westerns on single antennal pair protein extracts and allele-specific PCR from genomic DNA both show a segregating pattern of inheritance in laboratory and wild populations. Radio labelled (E)-11-tetradecenyl acetate binds to both fast and slow PBP forms in gel assays. Taken together, the genetic and biochemical data do not support the hypothesis that these PBPs are specific for each component of the E. postvittana pheromone. However, duplication of this PBP locus in the future might allow such diversification to evolve, as observed in the other species.

Amino Acid Sequence↗
PubMed2006

Mutations of the RET gene in isolated and syndromic Hirschsprung's disease in human disclose major and modifier alleles at a single locus.

BACKGROUND: In Hirschsprung's disease (HSCR), a hypomorphic allele of a major gene, RET, accounts for most isolated (non-syndromic) cases, along with other autosomal susceptibility loci under a multiplicative model. However, some syndromic forms of HSCR are monogenic entities, for which the disease causing gene is known. OBJECTIVE: To determine whether RET could be considered a modifier gene for the enteric phenotype on the background of a monogenic trait. METHODS: The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively. The RET locus was genotyped in 143 CCHS patients, among whom 44 had HSCR, and in 30 MWS patients, among whom 20 had HSCR. The distribution of alleles, genotypes, and haplotypes was compared within the different groups. To test the interaction in vivo, heterozygous mice were bred for a null allele of Phox2b and Ret genes. RESULTS: RET was shown to act as a modifier gene for the HSCR phenotype in patients with CCHS but not with MWS. The intestine of double heterozygote mice was indistinguishable from their littermates. A loss of over 50% of each gene function seemed necessary in the mouse model for an enteric phenotype to occur. CONCLUSIONS: In CCHS patients, the weak predisposing haplotype of the RET gene can be regarded as a quantitative trait, being a risk factor for the HSCR phenotype, while in MWS, for which the HSCR penetrance is high, the role of the RET predisposing haplotype is not significant. It seems likely that there are both RET dependent and RET independent HSCR cases.

Alleles↗
PubMed1997

A paternity case with apparently conflicting multilocus and single-locus DNA typing results.

A paternity case is presented in which DNA typing with thirteen variable number of tandem repeat (VNTR) systems was in apparent conflict with an initial multilocus DNA analysis using oligonucleotide probe (CAC)5. A dual approach was necessary, because the multilocus analysis yielded a proportion of aberrant nonmaternal offspring bands far too small and level of band-sharing too high for non-paternity. The case could finally be solved by reference to the joint likelihood ratio combining both approaches. Arguments are presented that summation of log likelihoods is indeed valid even if no information is available regarding linkage between the VNTR loci and the loci contributing to a multilocus DNA fingerprint.

DNA↗
PubMed1988

Methylglyoxal-bis(guanylhydrazone)-resistant Chinese hamster ovary cells: genetic evidence that more than a single locus controls uptake.

Chinese hamster ovary cells spontaneously resistant to the cytotoxic action of methylglyoxal-bis(guanylhydrazone) have been isolated in a multistep selection scheme. A low-level resistant isolate has been shown to be defective in the ability to accumulate the drug intracellularly. This was reflected in a 10-fold lower Vmax than wild-type cells for drug uptake as well as a slight enhancement of drug efflux. More highly resistant isolates selected from this low-level resistant isolate were totally deficient in the ability to take up the drug. A partial revertant, selected from this low-level resistant isolate, retained some change in the Vmax for uptake but lost the accelerated rate of efflux characteristic of the low-level resistant line. Genetic analysis by somatic cell hybridization indicated that the low-level resistant phenotype was recessive to the wild-type phenotype. In addition, the low-level resistant phenotype could be complemented by a previously isolated highly resistant cell also defective in drug uptake (Mandel and Flintoff (1978) J. Cell. Physiol., 97: 335-344). Taken together, these data suggest that more than one locus controls drug uptake in Chinese hamster ovary cells.

Adenosylmethionine Decarboxylase↗
PubMed1994

Linkage analyses in British pedigrees suggest a single locus for Darier disease and narrow the location to the interval between D12S105 and D12S129.

Darier disease is a dominantly inherited skin disorder in which there appears to be abnormal adhesion between keratinocytes. We and others have shown that the disease in some British pedigrees is closely linked to markers mapping to 12q23-q24.1. In the present study we have defined crossovers that enable us to narrow the location of the disease gene to the interval between the D12S105 and the D12S129 markers. This interval may be expected to be on the order of about 4 cM on the basis of linkage data obtained using the primary CEPH reference families. Our data provide further evidence for locus homogeneity: each of four large British pedigrees, two of which have previously been subjected to preliminary characterization, shows statistically significant evidence for linkage to markers mapping to 12q23-q24.1.

Chromosome Mapping↗
PubMed2003

Facultative sexual reproduction under frequency-dependent selection on a single locus.

The evolution of a facultative sexual strategy that simultaneously produced sexual and asexual individuals was studied theoretically, under negative frequency-dependence of fitness. The organism was considered to be diploid, characterized by two loci concerning fitness and determining sexual strategy, between which a certain degree of linkage existed. The locus concerning fitness was assumed to involve two alleles, resulting in three genotypes, the relative fitness of an individual being defined by a decreasing function of frequency of its own genotype on this locus in the population. The sexual reproductive strategy was considered to be determined by three alleles; asexual, obligate sexual and facultative sexual. Simulations under various linkages between loci and level of frequency dependence of fitness showed that a facultative sexual strategy was generally able to invade and increase in the population. In particular, when the level of frequency dependence was high to some degree, the facultative strain producing many sexual individuals tended to exclusively occupy the population. Namely, the frequency-dependent selection resulted in a predominance of obligate sexual strategy over asexual strategy, simultaneously causing a subordination of the former to the facultative sexual strategy. This indicated that the evolution of sex should be considered carefully with respect to the possibility of invasion of facultative sex.

Animals↗
PubMed1999

Single-locus tests of microsatellite evolution: multi-step mutations and constraints on allele size.

We evaluate some common simulation procedures as well as a recently developed likelihood method used for testing hypotheses regarding microsatellite evolution. Results from simulated data revealed that the tests for the detection of multi-step mutations in general have some power, whereas tests for the presence of constraints on the repeat number have only very limited power. The tests were applied to population data obtained from nine different baleen whale populations. High agreement was found between results obtained using the simulation-based approach and results obtained using a likelihood ratio test. In four of the nine population samples the tests rejected the one-step mutation model. In two instances the significant deviation was due to excess of heterozygosity and in two instances to a reduced level of heterozygosity relative to the expectations under the stepwise mutation model. The former significant deviation was consistent with occasional multi-step mutations, whereas the latter may indicate the presence of constraints on the number of repeats.

Alleles↗
PubMed1991

Multilocus and single locus minisatellite analysis in population biological studies.

In this review we describe the situations in which minisatellite analysis is of value to studies of population and evolutionary biology. Evolutionary and population biologists need to be able to quantify genetic relationships among individual organisms at many different levels, from close familial relationships to evolutionarily distant phylogenetic ones. The use of minisatellite markers is put into this context and compared with the other molecular biological techniques. Examples of the use of multilocus minisatellite analysis in population biology are described. The limitations of multilocus fingerprinting are presented, together with the potential advantages of locus-specific probes. The use of locus-specific probes in population biology is now often feasible due to the recent development of a cloning system which allows their efficient isolation. The availability of locus-specific probes should significantly expand the role of minisatellite markers in population biology.

Animals↗
PubMed1987

Cystic fibrosis--a single locus disease? Results of a population genetics study.

In a population genetics study of cystic fibrosis (CF), we investigated the state of health of 1276 first cousins of CF index patients. Six hundred seventy-five married aunts and uncles (siblings of CF index patients' mothers and fathers) who had at least one child were interviewed. In only 1 of these 675 families, three children of a total of eight had died of CF. If CF occurs more frequently than in 1 in 3000 newborn babies in our population, our investigation supports the hypothesis that CF is caused by mutations at more than one locus. We also determined that the evidence furnished by such a study of other, more uncommon autosomal recessive disorders is limited.

Cystic Fibrosis↗
PubMed1992

Single-locus control of saccharin intake in BXD/Ty recombinant inbred (RI) mice: some methodological implications for RI strain analysis.

The sac locus, with a major effect on saccharin preference, was discovered by Fuller (1974) in C57BL/6J (B6), DBA/2J (D2), and derived crosses, and is now supported in the BXD/Ty recombinant inbred (RI) series by a marked bimodal distribution in saccharin preference among 20 strains. The B6 allele led to increased saccharin preference compared to the D2 allele. Since the search for bimodal distributions reflecting major gene loci is an essential part of RI strain analysis, a new statistical method is proposed to test for bimodality, and comparisons are made to previously proposed methods. Another new RI method, quantitative trait loci (QTL) analysis, allows provisional detection and mapping of minor as well as major gene loci. Using this method as a screen, significant associations with saccharin preference were suggested with marker loci on portions of six chromosomes. One of these, the D12nyu1 locus on chromosome 12, was independently supported in a panel of standard (non-RI) inbred strains also tested for saccharin preference. It is unclear whether this reflects the sac locus.

Animals↗
PubMed1991

DNA single locus profiles: tests for the robustness of statistical procedures within the context of forensic science.

We describe a series of experiments, carried out on data from DNA profiles, which have been designed specifically to test the validity of the statistical procedures currently used in the Home Office Forensic Science Service. The tests address issues which have been the subject of topical debate, in particular those of representativeness and band independence. The results confirm the confidence which had already been placed in the established procedures. We recommend that all practitioners in the forensic field should carry out similar testing on their own data collections.

DNA Fingerprinting↗
PubMed1997

Bootstrap tests for specific hypotheses at single locus inbreeding coefficients.

Deviations of genotype distribution from Hardy-Weinberg expectations within a (sub)population can give valuable insight into the population structure, and can be quantified by means of F(is) values. Specific biological and/or genetical hypotheses regarding F(is) require particular statistical procedures to be able to perform the test with high power. The bootstrap offers a convenient way to test against a broad range of alternative hypotheses. It enables: a) comparison of an observed F(is) with any expected value between -1 and 1, and b) comparison of two or more observed F(is) values. However, it fails under numerous situations, and great caution should be taken before applying the bootstrap to estimate confidence intervals of F(is). We discuss under which conditions the bootstrap gives reliable results.

Gene Frequency↗
PubMed1999

Nonlinear frequency-dependent selection at a single locus with two alleles and two phenotypes.

The paper investigates the discrete frequency dynamics of two phenotype diploid models where genotypic fitness is an exponential function of the expected payoff in the matrix game. Phenotypic and genotypic equilibria are defined and their stability compared to frequency-dependent selection models based on linear fitness when there are two possible phenotypes in the population. In particular, it is shown that stable equilibria of both types can exist in the same nonlinear model. It is also shown that period-doubling bifurcations emerge when there is sufficient selection in favor of interactions between different phenotypes.

Alleles↗