Frequency of the ESD*5 allele in a Spanish population

The red blood cell esterase D (ESD) polymorphism was studied by means of IEF in a North-East Spanish population (Barcelona). Gene frequencies in 430 unrelated individuals were ESD*1: 0.888, ESD*2: 0.091 and ESD*5: 0.021. Our data confirm previous results showing that ESD*5 occurs in polymorphic frequency and has a Caucasian origin.     

Further studies of the plasma alpha 1 B-glycoprotein polymorphism: two new alleles and allele frequencies in Caucasians and in American blacks

Two new alleles (A1 B*3 and A1 B*4) of human plasma alpha 1 B-glycoprotein (alpha 1 B) were reported. alpha 1 B phenotyping was done by using either a simple method of two-dimensional (2-D) agarose gel-horizontal polyacrylamide gel electrophoresis (PAGE) followed by protein staining or by one-dimensional horizontal PAGE and immunoblotting. Seven different alpha 1 B phenotypes (1-1, 1-2, 1-3, 1-4, 2-2, 2-3 and 3-3) were observed; phenotypes 1-3 and 1-4 were differentiated from each other only by the 2-D method. The respective frequencies Af A1 B*1, A1 B*2, A1 B*3 and A1 B*4 alleles in the studied populations were estimated as follows: American Blacks (New York) 0.732, 0.204, 0.064, 0; American Whites (New York) 0.947, 0.053; Czechs (M?lník) 0.964, 0.034, 0, 0.002; Slovaks (Bratislava and Trencin) 0.977, 0.023, 0, 0. The population of American Blacks showed a much higher degree of alpha 1 B polymorphism (polymorphism information content = 0.37) than the Caucasian populations that have been studied.     

Frequency of the ESD*5 allele in three ethnic groups in Minnesota

Summary Detection of the ESD*5 gene products was simplified by the use of isoelectric focusing (IEF). Gene frequencies for ESD*5 in whites, blacks and Amerindians from the State of Minnesota were 0.019, 0.002 and 0.000, respectively. The gene frequencies observed in the white data set were similar to those reported for European whites.     

The esterase D polymorphism by ultrathin layer isoelectric-focusing: frequency of the EsD5 allele in the population of Rome

The distribution of EsD phenotypes in the population of Rome was investigated by cellulose-acetate electrophoresis and isoelectric-focusing. The gene frequencies were found to be: EsD1 = 0.8451, EsD2 = 0.1363, EsD5 = 0.0186. These frequencies were compared with those reported in other populations.     

Genetic polymorphism of alpha-2-HS-glycoprotein: four new alleles and allele frequencies in Japanese

alpha 2-HS-glycoprotein (AHSG) phenotyping was done in 655 Japanese from the Goto Islands, western Japan, using isoelectric focusing followed by immunoblotting. Four new AHSG alleles were encountered, AHSG*G1-G4, whose genetic transmissions were established in family studies. The allele frequencies were: AHSG*1 = 0.7221; AHSG*2 = 0.2748, and AHSG*G1-G4 = 0.0008, respectively.     

Alkaline opening of imidazole ring of 7-methylguanosine. 2. Further studies on reaction mechanisms and products

High performance liquid chromatography (HPLC) was used to follow the kinetics of the alkaline induced opening of the imidazole ring of 7-methylguanosine (7-meGuo). The kinetics show an initial rapid formation of a major transient intermediate and some minor products that were chromato-graphically separable into seven peaks. This phase of the reaction is followed by the formation of a dominant pyrimidine derivative whose liquid chromatography retention time in a 6% methanol, 0.01 M NH₄H₂PO₄ (pH 5.1) solvent is 6 min; during the rest of the reaction time this dominant species was progressively converted to a co-dominant species that has a 4.5-min column retention. Mass spectroscopy confirmed the existence of two species of ring opened 7-methylguanine (7-meGua), one formylated and another deformylated. Schiff's reaction demonstrated that the species in the second HPLC peak is the formylated one. The ring opened 7-methylguanine (rom⁷Gua) released by formamidopyrimidine (FAPy)-DNA glycosylase was shown to coelute with the formylated species. These results demonstrate that the enzyme excises formylated rom⁷Gua from DNA Analysis of rom⁷Guo by NMR showed that there are two signals assignable to methyl protons and two to formyl protons. These chemical shifts were interpreted as being due to the opening of the imidazole ring at two sites and to the formation of formylated and deformylated rom⁷Gua.     

The novel allele (3R) of the VNTR polymorphism in the XRCC5 promoter region dramatically decreases the gene expression

Polymorphism of variable number of tandem repeats (VNTR) in the promoter region of X-ray repair cross-complementing 5 (MIM: 194364, XRCC5; rs6147172) was reported. The aim of the present study is to evaluate the influence of this polymorphism on XRCC5 mRNA levels. Genotypes of XRCC5 VNTR were determined by high resolution of melting analysis (HRMA). The quantitative XRCC5 mRNA expression (compared to ß-actin expression) among 0R/1R, 1R/2R, and 1R/3R genotypes was investigated. There was a negative correlation between the overall number of tandem repeats and XRCC5 expression (r = ?0.965, df = 7, P < 0.001). The mRNA level of XRCC5 decreased as function of number of tandem repeats. The 3R allele of the VNTR polymorphism in the XRCC5 promoter region dramatically decreases the gene expression.     

The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations.

Application of uniform methods for measuring the apolipoprotein (apo) E polymorphism and plasma cholesterol levels in nine populations (Tyrolean, Sudanese, Indian, Chinese, Japanese, Hungarian, Icelandic, Finnish, and Malay) revealed significant heterogeneity among them in apo E type frequencies and mean cholesterol levels. The major apo E types in all populations were E3/2 (frequency range from 7.0% in Indians to 16.9% in Malays), E3/3 (frequency range from 39.8% in Sudanese to 72.1% in Japanese), and E3/4 (frequency range from 11.3% in Japanese to 35.9% in Sudanese). Mean cholesterol levels ranged from 144.2 mg/dl in the Sudanese to 228.5 mg/dl in the Icelandics. Two-way analysis of variance of the effect of population and apo E type on cholesterol levels showed no significantly interaction effect, indicating that the effects of apo E type on cholesterol levels do not differ significantly among the populations. The overall average excess for the epsilon 2 allele was -14.12 mg/dl (range -31.63 to -8.82 mg/dl); for the epsilon 3 allele, 0.04 mg/dl (range -1.87 to 1.58 mg/dl; and for the epsilon 4 allele, 8.14 mg/dl (range -1.71 to 13.31 mg/dl). Despite the apparent heterogeneity in these values, especially for the epsilon 4 allele, comparison of the average excesses by a method of repeated sampling with random permutations revealed no significant difference in effects among populations. These data indicate that a given apo E allele acts in a relatively uniform manner in different populations despite differences in genetic background and environmental factors.     

The DNA restriction endonuclease of Escherichia coli B. II. Further studies of the structure of DNA intermediates and products

The DNA intermediates and final products formed by the Type I restriction endonuclease, EcoB, were further characterized. DNA cleaved on only one strand (hemi-restricted DNA) contains gaps of approximately 70-100 nucleotides, while the fully restricted products contain 3'-single-stranded tails averaging approximately 70-100 nucleotides for each strand cleaved. The gaps and tails are formed with the release of an equal number of nucleotides as small oligonucleotides that are soluble in acid. After purification, neither the hemi-restricted nor the fully restricted DNAs are cleaved again by EcoB. There is no apparent specificity for which strand of a duplex is initially cleaved by EcoB, nor is there specificity with respect to the composition of the 3'-terminal nucleotide formed on the DNA or the 3'- or 5'-terminal nucleotides of the acid-soluble oligonucleotides released during DNA cleavage. The structure formed at the 5' terminus of the DNA product which blocks phosphorylation by T4 polynucleotide kinase remains unknown, but its removal with phage lambda exonuclease allows at least some reutilization of recognition sites by EcoB as well as phosphorylation of the newly formed 5' termini. To explain the complex mechanism of this enzyme, it is suggested that the unidentified 5'-tails prevent wasteful rerestriction from occurring, whereas the 3'-single-stranded tails create DNA which, when nonhomologous to chromosomal DNA, cannot be rescued because such tails are not substrate for DNA polymerases. However, when homologous chromosomal DNA exists, the randomly cleaved large fragments with these tails can easily be assimilated by recA-mediated genetic recombination, thus stimulating DNA exchange between related organisms.     

TaqIB allele polymorphism of the dopamine receptor D2 gene in patients with endogenous psychoses

The genotype at theTaqIB locus of the dopamine receptor D2 (DRD2) gene was established by PCR in 113 healthy donors and 340 patients with endogenous psychoses. The allele and genotype frequencies in patients with affective psychoses significantly differed from those in controls and in patients with schizophrenia. The proportion of B2/B2 homozygotes decreased with increasing contribution of the affective component to the clinical manifestation of schizo-affective and affective disorders. TheTaqIB polymorphism was assumed to play a role in mood aberrations in patients with mental disorders.     

Further studies on non-H-2 histocompatibility alloantibodies in the mouse

Immunofluorescence tests indicate that alloantibodies specific for mouse histocompatibility antigens H-1^a, H-3^a, and H-13^a have been produced, using four different immunizations. Furthermore, an immunization employing donors and recipients which were H-2^k at the MHC produced stronger anti-H-3^a and anti-H-13^a than did immunizations where donors and recipients were H-2^b at the MHC.     

A 5' intronic splice site polymorphism leads to a null allele of the P2X7 gene in 1-2% of the Caucasian population

The P2X(7) gene is important for the innate immune response but known polymorphisms do not explain all subjects with loss of P2X(7) function. A splice site mutation (g-->t) was found at position +1 of the first intron of the P2X(7) gene in 7 of 336 Caucasians and 1 of 39 subjects of Indian ethnicity. All eight subjects were heterozygous for the uncommon 1513A-->C polymorphism of the P2X(7) gene. RT-PCR and sequencing showed the splice site mutation was on the 1513C allele in the Caucasians and on the 1513A allele in the Indian subject. The splice site mutation is an inherited polymorphism and gives rise to a P2X(7) null allele in 1-2% of the Caucasian population.     

Further studies on the ethanol antagonism exhibited by 2(2-chloro-5-trifluoromethyl phenylimino) imidazolidine (St 587)

A lipid soluble alpha 1-adrenoceptor agonist 2-(2-chloro-5-trifluoromethyl phenylimino) imidazolidine (St 587) dose-dependently antagonized the hypnotic, hypothermic and respiratory depressant effects of ethanol in C57B1/6 mice. This effect was present whether St 587 was given before or after ethanol. St 587 did not block the pentobarbitone-induced hypnosis. It also did not influence the elimination of ethanol. Combined treatment with a subhypnotic dose of ethanol and St 587 resulted in marked hyperactivity in mice. This effect was completely abolished by pimozide pretreatment. It was inferred that the dopamine released from brain areas by this dose of ethanol together with the norepinephrine receptor activation offered by St 587 resulted in this hyperactivity. Cirazoline, a more potent alpha 1-adrenoceptor agonist than St 587 was relatively more effective than the latter in blocking the ethanol-induced hypnosis in mice. It seems that alpha 1-adrenoceptor stimulation is a major contributing factor to the ethanol antagonism exerted by St 587. This drug might prove to be useful in the treatment of acute ethanol intoxication and in understanding the mode of action of ethanol.     

The geographic spread of the CCR5 Delta32 HIV-resistance allele

The Delta32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Delta32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Delta32 allele, we implemented a spatially explicit model of the spread of Delta32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Delta32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Delta32 allele is consistent with previous reports of a strong selective advantage (>10%) for Delta32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Delta32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Delta32 allele and establish a general methodology for studying the geographic distribution of selected alleles.