Single Mendelian Gene Research Articles

Genetics of CM-proteins (A-hordeins) in barley

The CM-proteins, which are the main components of the A-hordeins, include four previously described proteins (CMa-1, CMb-1, CMc-1, CMd-1), plus a new one, CMe-1, which has been tentatively included in this group on the basis of its solubility properties and electrophoretic mobility. The variability of the five proteins has been investigated among 38 Hordeum vulgare cultivars and 17 H. spontaneum accessions. Proteins CMa-1, CMc-1 and CMd-1 were invariant within the cultivated species; CMd was also invariant in the wild one. The inheritance of variants CMb-1/CMb-2 and CMe-1/CMe-2,2' was studied in a cross H. spontaneum x H. vulgare. The first two proteins were inherited as codominantly expressed allelic variations of a single mendelian gene. Components CMe-2,2' were jointly inherited and codominantly expressed with respect to CMe-1. Gene CMb and gene(s) CMe were found to be unlinked. The chromosomal locations of genes encoding CM-proteins were investigated using wheat-barley addition lines. Genes CMa and CMc were associated with chromosome 1, and genes CMb and CMd with chromosome 4. These gene locations further support the proposed homoeology of chromosomes 1 and 4 of barley with chromosomes groups 7 and 4 of wheat, respectively. Gene(s) CMe has been assigned to chromosome 3 of barley. The accumulation of protein CMe-1 is totally blocked in the "high lysine" mutant Riso 1508 and partially so in the high lysine barley Hiproly.

Inheritance of resistance to benomyl in isolates of Venturia inaequalis from Israel*

Ten single‐spore cultures of benomyl‐resistant Venturia inaequalis were isolated from apple scab lesions at two sites in Israel. According to the ability of the isolates to germinate and grow at varying benomyl concentrations, three levels of resistance were determined in vitro: two moderately resistant (MR) isolates were resistant to 5 μg/ml but sensitive to 50 μg/ml benomyl; five highly resistant (HR) isolates, grew and sporulated at 50 μg/ml more slowly than at 5 μg/ml; and three isolates with very high resistance (VHR) grew and sporulated as freely at 50 μg/ml as at 5 μg/ml. Crosses between resistant isolates and sensitive wild types, as well as between different resistant isolates, showed that the various levels of benomyl resistance are conferred by three allelic mutations that constitute a polymorphic series in a single Mendelian gene. In these isolates benomyl resistance is not affected by modifying genes or cytoplasmic components.

Genetic control of lipid transport in mice. II. Genes controlling structure of high density lipoproteins.

Genetic factors controlling the structure of high density lipoproteins (HDL) in mice have been examined. Surveys of inbred strains of mice revealed genetic structural variations of the two major apolipoproteins of mouse HDL, apolipoproteins A-I and A-II. The structural variations alter the charge of the proteins as judged by isoelectric focusing of HDL under denaturing conditions. The structural variations are inherited as single Mendelian genes exhibiting co-dominant expression. The structural gene for mouse apolipoprotein A-II, designated Alp-2, resides on mouse chromosome 1, tightly linked to Ly-m20, a lymphocyte alloantigen locus. Previous studies, as well as our results, suggest that the structural gene for mouse apolipoprotein A-I, designated Alp-1, is on mouse chromosome 9. The genetic structural variation for apo-A-I results in a shift in the charge of the entire family of apo-A-I isoforms, indicating that they are all encoded by a common structural gene. The structure of intact HDL, examined primarily by electrophoretic techniques, exhibits numerous and complex phenotypes among different strains of mice. One variation, controlling the density and possibly the size of HDL, has been studied in two sets of recombinant inbred strains of mice. The results indicate that the variation is controlled by a single major gene that is either tightly linked to or identical with the Alp-2 gene on chromosome 1. In addition to structural variation, inbred strains of mice exhibited considerable quantitative variation of plasma HDL. Thus, the mouse provides a useful model system for examining the genetic control of mammalian HDL structure and regulation.

Allele-specific suppression of a cell cycle mutant of S. cerevisiae

A cell cycle (cdc) mutant of Saccharomyces cerevisiae is described which fails to complement cdc27-1 described by Hartwell et al. 1973), and is designated cdc27-47. Whereas cdc27-1 behaves as a single Mendelian gene (Hartwell et al. 1973), cdc27-47 requires the presence of an additional unlinked gene for expression of temperature-sensitivity. This gene, designated sts47, is present in some, but not all, laboratory wild-type strains. Expression of cdc27-1 is not influenced by STS47. A model for suppression is proposed involving the modification of conformation within a structural or enzyme complex.

Inheritance and mapping of storage protein genes in Pisum sativum L.

One and two-dimensional sodium dodecyl sulphate Polyacrylamide gel electrophoretic techniques have been used to follow the inheritance of legumin and convicilin subunits in crosses of various pea lines. The major legumin acidic subunits behaved as products of a single Mendelian gene with at least five different possible alleles. Independent segregation of a minor “big” legumin acidic subunit and the acidic and basic subunits of “small” legumin were observed, suggesting that while the main legumin subunits are produced from a set of closely linked genes at a single locus, further weakly expressed legumin genes are present at other loci. Convicilin subunits behaved as the products of a single Mendelian gene with at least three allelic forms. Genetic analysis of F2 seeds and plants from crosses of pea lines was used to map the major legumin gene (Lg-1) to a locus near the r-tl segment of chromosome 7 and the convicilin gene (Cvc) to a locus between s and k on chromosome 2.

Linkage relationships between genes controlling seed proteins in French bean

The inheritance of phaseolin and globulin-2 (G2)/albumin polypeptides was investigated in crosses involving varieties which exhibited the three electrophoretic banding patterns of phaseolin found in French bean. 'Total' seed protein extracts of single seeds of the F1 and F2 generations from the crosses: 'Sanilac' × 'Contender', 'BBL 240' × 'Contender', and 'Sanilac' × 'BBL 240' were analyzed by two-dimensional electrophoresis. Segregation of the genes controlling phaseolin and G2/albumin polypeptides, and those controlling a further five groups of seed proteins (A, B, D, E, and F) were observed. No recombinant electrophoretic phenotypes were seen for phaseolin or G2/albumin polypeptides suggesting that the genes controlling each of these groups of polypeptides are closely linked and segregate like single Mendelian genes. The phaseolin genes and G2/albumin genes were not linked to each other. The group of genes controlling phaseolin polypeptides were linked to those controlling group B proteins, and those controlling G2/albumin polypeptides were linked to those controlling group F proteins.

Genetic variation of milk proteins in mice.

A survey for qualitative and quantitative variation in milk proteins from 58 inbred strains of mice revealed two electrophoretic variants. One is in a whey acidic protein of milk of YBR mice and the other is in a curd protein of the Asian house mouse, Mus musculus castaneus. The whey acidic protein variant is shown to be under the control of a single Mendelian autosomal gene with alleles expressed in a codominant manner. This gene is designated Wap, is not identical to Eg, is not X linked, and is either unlinked or loosely linked to the coat color genes a and b.

Genetic mapping of xenotropic murine leukemia virus-inducing loci in five mouse strains.

A single mendelian gene was identified for induction of the endogenous xenotropic murine leukemia virus in five mouse strains (C57BL/10, C57L, C57BR, AKR, and BALB/c). This locus, designated Bxv-1, mapped to the same site on chromosome 1 in all strains: Id-1-Pep-3-[Bxv-1-Lp]. Thus, inducibility loci for xenotropic virus are more limited in number and chromosomal distribution than ecotropic inducibility loci. Virus expression in mice with Bxv-1 was induced by treatment of fibroblasts with 5-iododeoxyuridine or by exposure of spleen cells to a B cell mitogen, bacterial lipopolysaccharide. An analysis of the hamster X mouse somatic cell hybrids indicated that chromosome 1, alone, was sufficient for virus induction.

A MUTATOR AFFECTING THE REGION OF THE ISO-1-CYTOCHROME c GENE IN YEAST

The mutator gene DEL1 in the yeast Saccharomyces cerevisiae causes a high rate of formation of multisite mutations that encompass the following three adjacent genes: CYC1, which determines the structure of iso-1-cytochrome c; RAD7, which controls UV sensitivity; and OSM1, which controls osomotic sensitivity. The simplest hypothesis is that these multisite mutations are deletions, although it has not been excluded that they may involve other types of gross chromosomal aberrations. In contrast, normal strains do not produce such multisite mutations even after mutagenic treatments. The multisite mutations arise at a rate of approximately 10(-5) to 10(-6) per cell per division in DEL1 strains, which is much higher than rates observed for mutation of genes in normal strains. For example, normal strains produce all types of cyc1 mutants at a low rate of approximately 10(-8) to 10(-9). No evidence for multisite mutations was obtained upon analysis of numerous spontaneous ade1, ade2, met2 and met15 mutants isolated in a DEL1 strain. DEL1 appears to be both cis- and trans-dominant. The location of the DEL1 gene and the lack of effect on other genes suggest that the mutator acts only on a region adjacent to itself.

Moloney leukemia virus gene expression and gene amplification in preleukemic and leukemic BALB/Mo mice

Mice carrying the exogenous Moloney leukemia virus (M-MuLV) as an endogenous virus have been derived previously. This mouse strain (BALB/Mo) transmits the virus as a single Mendelian gene (Mov-1 locus) from one generation to the next. Molecular hybridization experiments were performed to identify the organs in which the M-MuLV gene is activated during postnatal life of BALB/Mo mice and to determine the age-dependent onset of M-MuLV gene expression. Spleen and thymus cells of BALB/Mo mice synthesize M-MuLV-specific RNA soon after birth and virus gene expression reaches high levels at 3–4 weeks of age. A substantial further increase in virus gene expression is not observed in leukemic tissues of older animals. Other organs, such as liver, brain, and kidneys, do not express M-MuLV-specific RNA throughout the animals' life. These observations define lymphatic tissues (spleen and thymus) as the target organs of M-MuLV expression in BALB/Mo mice. Virus gene expression was correlated with somatic amplification of M-MuLV-specific DNA sequences during the preleukemic and leukemic phase of the animals' life. DNA amplification occurs in two steps in target tissues of BALB/Mo mice. A first step to approximately two copies per haploid genome equivalent is observed in preleukemic mice and a second step to three to four copies is observed in leukemic tissues. Nontarget tissues carry one copy of M-MuLV-specific DNA sequences regardless of the age of the animal. These results suggest that M-MuLV-specific gene expression is not sufficient for leukemic transformation and is related to virus-specific DNA amplification in preleukemic animals. A second amplification of M-MuLV DNA sequences appears to be related to leukemic transformation.

Genetic transmission of Moloney leukemia virus: mapping of the chromosomal integration site.

Mice genetically transmitting the exogenous Moloney leukemia virus (Balb/Mo) have been previously derived. These animals carried one copy of Moloney virus DNA (M-MuLV) in their germ line and transmitted the virus as a single Mendelian gene to the next generation. Homozygous BALB/Mo mice were used to genetically map the M-MuLV locus. Embryo fibroblasts were fused to established Chinese hamster cells and somatic cell hybrids were selected. Segregation of mouse chromosomal markers in the hybrids was correlated to the loss of M-MuLV-specific sequences as detected by molecular hybridization. Of 15 isozymes located on different mouse chromosomes only triosephosphate isomerase segregated syntenic with the M-MuLV gene, suggesting that the virus was integrated on chromosome No. 6. This was confirmed by sexual genetic experiments analyzing segregation of Moloney viremia and two markers on chromosome 6 and 15, respectively. The results show that M-MuLV expression is linked to wa-1 on chromosome 6 at a distance of about 30 map units. These data define a new genetic locus, Mov-1, representing the structural gene of M-MuLV in BALB/Mo mice.

Genetic control of igG2a production in the response to sheep erythrocytes

A low IgG2a response in B10 mice during the primary response to sheep red blood cells (SRBC) is described. Analysis of the response in B10 × BALB/c hybrid progenies and in congenic strains indicates that this low response is a dominant phenotype placed under the control of a single Mendelian gene or a group of closely linked genes. This gene(s) is neither linked to CH allotypes orH2 haplotypes, nor is it sex-linked. It can be considered as an isotype- and antigenspecific regulatory gene of the immune response.

Suppression of IgE antibody production in SJL mice. I. Nonspecific suppressor T cells.

High titer and persistent antihapten IgE production in SJL mice can be obtained using appropriate immunization and radiation. Nonirradiated mice rapidly terminate this antihapten IgE production. Radiation was not necessary to prolong antihapten IgE production in other strains of mice. Termination can be obtained even in irradiated SJL mice by transferring normal SJL spleen cells. That the suppressor cells are T cells is shown by using thymocytes or cells treated with anti-Thy 1.2 and complement. No appreciable suppressive effect by normal spleen cells could be demonstrated on IgG1 production in SJL mice. The characteristic of low and transient IgE antibody response in SJL mice is inherited as a recessive trait controlled by a single Mendelian autosomal gene and is not linked to the H-2-gene complex. This characteristic does not depend on the infectivity of Nippostrongylus brasiliensis, the effect of anticarrier antibody, or the recognition of antigen.

Heritable Variation in a Polypeptide Subunit of the Major Storage Protein of the Bean, Phaseolus vulgaris L.

Electrophoretic analysis of the major seed protein, G1 globulin, from four strains of Phaseolus vulgaris L. revealed a three-banded pattern for two strains having a high methionine content (BBL 240 and PI 302,542). The other two strains (PI 207,227 and PI 229,815) known to have a lower seed methionine content, had a two-banded subunit pattern for the G1 globulin. Analytical ultracentrifugation confirmed that globulin from the two-banded strains underwent pH-dependent reversible dissociation similar to that previously found for a three-banded cultivar; additionally, the protomer molecular weight showed that three subunits of about 50,000 molecular weight each were present in the G1 globulin of the two-banded strain. Gel patterns of G1 globulin from the two strains used as parents, BBL 240 and PI 229,815, showed differences in the largest subunit, which appeared as either a 53,000 molecular weight polypeptide known to be present in the three-banded strain, or as a shorter polypeptide having a molecular weight close to 47,000. Analysis of G1 protein from portions of single hybrid seeds showed a banding pattern intermediate between the two- and three-banded types. The subunit pattern from all seeds with intermediate-banded parents segregated in a manner consistent with that expected for control of the polypeptide by a single Mendelian gene. The remaining portions of the seeds were grown to confirm that they represented true crosses. The procedures used are essentially nondestructive, and can be used as a basis for selecting seeds having different protein characters.

Isolation and properties of a thymidylate-less mutant in Saccharomyces cerevisiae.

A mutant, tmp3, has been isolated in Saccharomyces cerevisiae. Genetic and physiological analysis show that a single mendelian gene controls the multiple requirements for thymidylate, methionine, adenine and histidine and a neutral cytoplasmic petite character. Crude extracts of this mutant present a 60% decrease of serine transhydroxymethylase specific activity as compared to a wild-type strain.

Genetic control of "flor" formation by Saccharomyces.

The results described indicate that in Saccharomyces sp. the formation of "flor" is under the control of a single Mendelian gene for which is proposed the symbol "Fl."

New Type of Ultraviolet Light-Sensitive Mutation in Yeast

Four temperature-sensitive ultraviolet light-sensitive mutants of yeast have been isolated. All four mutations show complementation in diploid cells and the phenotypes associated with the rad (ts) mutations are the result of the activities of single mendelian genes.

Genetic and metabolic bases of two "albino" phenotypes in the leopard frog, Rana pipiens.

AbstractPreliminary characterizations of albino Rana pipiens from two widely separated geographic origins, Mexico and Michigan, indicated that different metabolic basés underlie the albino phenotype.Albinism in the Mexican frogs was shown to result from a single Mendelian recessive gene, am (amelanotic), and appeared to involve a biochemical failure of the pigment synthesizing system. Melanophores were present in am/am integument which exhibited tyrosinase activity when provided with exogenous tyrosine or L‐DOPA. The tyrosinase activity of am/am melanophores showed greater thermolability than did that of wild type malanophores.The “albinism” of tadpoles collected in Michigan was only partial, and was associated with a highly pleiotropic syndrome, abnormal patterning of chromatophore distributions, and metamorphic failure. Poor pigmentation of integumental melanophores appeared associated in part with inhibitors of melanogenesis. Genetic data on the possible mode of inheritance are not yet available.

The genetic control of the two types of mannan produced by Saccharomyces cerevisiae.

The two mannans formed by different strains of Saccharomyces cerevisiae give proton magnetic resonance spectra (spectral types A and B), which suggests that they differ principally in the presence of a-(1 → 3)-linked mannopyranosyl end units of the side chains of the more complex type (giving spectral type B). The presence or absence of such end units was under the control of a single mendelian gene, since the two types of mannan segregated independently during sporulation. The gene controlling this type of mannan produced was apparently not linked to those controlling the requirements for adenine, uracil, leucine, or histidine. The implications of the findings concerning the mechanism of biosynthesis of yeast mannan are discussed.

Ultraviolet-light sensitive mutants of Aspergillus nidulans

14 mutants of Aspergillus nidulans were isolated which were more sensitive to the lethal effects of UV light than wild-type strains. Haploidization analysis of 6 mutants showed that 4 are on linkage group IV, 1 on V and the other on II or VIII. The sensitivity of 6 mutants to nitrous acid was tested and it was found that ranking in terms of UV sensitivity paralleled ranking in terms of nitrous acid sensitivity. No effects on the frequency of meiotic intergenic recombination were found in crosses heterozygous for 7 of the mutants. 1 of these mutants was tested in a homozygous cross and again no effects were observed. The mutations were inherited as single mendelian genes and the survival of diploid conidia after UV irradiation suggested that they were also recessive. 5 mutants had an effect on ascospore development. Viable ascospores were recovered from crosses of these mutant strains in reduced numbers.