SEARCH · PubMed Health
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.
The frequency of HinfI RFLP and dinucleotide (CA) repeat polymorphism for the WT1 located to chromosome 11p13 among the Japanese were estimated. Each polymorphism showed high frequency of heterozygosity and segregated independently.
The intra-species differentiation of Pseudomonas aeruginosa was analysed by comparing the polymorphism of esterases by conventional polyacrylamide-agarose gel electrophoresis, the physicochemical properties of the variants of the major esterase P3 and the restriction fragment length polymorphism of ribosomal RNA gene regions (ribotyping) to O-serotyping for several panels of strains selected from among a series of 257 clinical isolates and two references strains, (ATCC nos. 10145 and 27853). The electrophoretic variation of four main kinds of esterase (P1-P4) and 11 additional esterases distinguished by their spectra of hydrolytic activity with synthetic substrates and by their sensitivity to di-isopropylfluorophosphate, allowed the discrimination of 67 zymotypes. Thirty-two esterase P3 variants were characterized by their pI, electrophoretic mobilities and titration curve analyses. They were distributed into two groups which, by these molecular criteria, seem to be distantly related. Combination of the patterns resulting from HindIII, EcoRI and BclI restriction endonuclease digestions allowed the discrimination of 33 ribotypes among 134 strains. The strains exhibiting esterase P3 variants of group 2 presented a distinct ribotype and belonged to serotype (O)12. They could constitute a distinct group within the species. For the majority of the strains, the absence of correlation between zymotype, ribotype and serotype argues for a high level of heterogeneity within P. aeruginosa and indicates that the parallel use of the first two methods represent a potential tool for epidemiological study.
OBJECTIVE: Androgen insensitivity syndrome is a disorder of male sexual development which results in varying degrees of undervirilization in 46XY individuals with functional testes. In the most severe form, complete androgen insensitivity syndrome (CAIS), patients have a normal female appearance. Although CAIS is not life-threatening, affected individuals are infertile and require counselling, gonadectomy, hormone therapy, and sometimes vaginoplasty. Many families therefore request genetic counselling. Defects in the androgen receptor gene account for most if not all cases of CAIS. The purpose of this study was to evaluate the use of the polyglutamine and polyglycine trinucleotide repeat polymorphisms in the first exon of the androgen receptor gene for carrier status determination in three CAIS families. In two of these families novel mutations in the androgen receptor gene were subsequently identified which allowed confirmation of carrier status and also a prenatal diagnosis to be made in one family. PATIENTS: Three CAIS families were studied. The index cases all presented with a clinical phenotype typical of CAIS. MEASUREMENTS: Family members were typed initially for the polyglutamine repeat. In one family this was not informative and the polyglycine repeat was therefore studied. In this and one further family, the androgen receptor gene was sequenced to identify the mutation causing the CAIS. RESULTS: On the basis of information from trinucleotide repeat analysis carrier status could be assessed in each family. In one family, evidence for somatic instability of the polyglutamine repeat was found. In the same family, a novel mutation in the androgen receptor gene, which substituted valine for leucine 881, was identified. Other family members were subsequently typed for the mutation and a prenatal diagnosis was performed. A novel mutation was also identified in a second family substituting the glycine codon at position 371 with a stop codon. Other family members were typed for this mutation. CONCLUSIONS: Both the polyglutamine and polyglycine repeat polymorphisms are useful for the genetic counselling of complete androgen insensitivity syndrome families. In some cases, however, where the family history is limited, more precise information can be provided only once the androgen receptor mutation causing the complete androgen insensitivity syndrome has been identified.
Seven DNA markers from five genes and one chromosomal region were analysed in Mongolian population using the polymerase chain reaction. The frequencies of alleles of the polymorphisms detected with HindIII in the HBG-2, AvaII in the HBB, MspI and XbaI in the Apo-B, PstI in the D7S8, HincII in the LDLR and allele frequency of the minisatellite fragment in the AT-3 have been determined. The results of the RELP for Apo-B(MspI), LDLR, D7S8 and AT-3 are obtained for the first time among Mongoloids. DNA markers studied demonstrated high level of polymorphisms in the population of Mongolia, except for XbaI and MspI restriction sites at the Apo-B locus. The data obtained for Mongolian population and the literature data were compared.
We have investigated restriction fragment length polymorphism (RFLP) of HLA and non-HLA regions of the genome in the homogeneous Danish population. Insulin-dependent diabetes mellitus (IDDM) patients and healthy individuals were selected for being HLA-DR 3/4 heterozygous to evaluate the influence of genes other than DR on disease susceptibility. Five different probes were used: HLA alpha and beta DQ (chromosome 6), the Ins 310 genomic fragment which detects a polymorphic region 5' to the insulin gene (chromosome 11), and cDNA for the constant regions of the T cell receptor alpha and beta genes (chromosomes 14 and 7). Fifteen cells homozygous for the HLA-D region were used to obtain reference DNA patterns. This allowed us to describe four splits among the HLA-DQw3 haplotypes (DQw3.1 to DQw3.4). The two new haplotypes DQw3.3 and DQw3.4 do not code for the TA10 serological marker which is found on DQw3.1 positive cells. One-hundred per cent of IDDM patients were typed as DQw3.2 versus 68 per cent for controls (p = 0.003). However, our results do not indicate a role for the Ins 310 or for the alpha DX locus region in IDDM susceptibility, in contrast to previous reports by others. The restriction enzymes that we have used did not reveal significant differences between DNA patterns of patients and controls with probes for the constant region of the T cell receptor genes.
Methods for identity testing are described that enable extraction of DNA from biological samples, determination of the quantity of human DNA, and genetic analyses of the materials using restriction fragment length polymorphism (RFLP) typing and/or amplified fragment length polymorphism (AMP-FLP) typing of PCR products. The salient features of the procedures are simplicity, manual typing, nonradioactive chemiluminescent assays or silver staining for detection, and low cost. Most application-oriented laboratories involved in forensic and/or paternity testing should be able to implement these procedures.
We describe a common single-base polymorphism of the KIT gene that alters both SmaI and BstNI restriction sites, but is most easily detected as a single-strand conformation polymorphism (SSCP) using the polymerase chain reaction (PCR).
This note gives some further useful properties of the constant fitness selection model for multiple alleles which pertain to the effects of adding a new allele to n preexisting alleles in stable equilibrium. In particular the conditions are derived for the establishment of a stable equilibrium involving all n + 1 alleles. For 3 alleles (i.e. n = 2) I give a complete qualitative solution, including the case of the replacement of one diallelic polymorphism by another. As an application I discuss a possible mechanism for the evolution of polymorphism using Monte Carlo methods similar to Lewontin, Ginzburg and Tuljapurkar (1978).
A comparative study of frequencies and types of Q-polymorphic variants in seven autosome pairs (3, 4, 13-15, 21, and 22) was performed in three steppe Mongoloid populations of Central Asia (Kazakhs, Dunghans, Mongolians) and three highland Kirghiz populations of Pamir and Tien-Shan. The three steppe Mongoloid populations showed statistically significant homogeneity both in the frequency of Q-polymorphic variants and the distribution of homo- and heteromorphs, with complete agreement of observed frequencies with those theoretically predicted by the law of Hardy-Weinberg. Similar homogeneity was revealed in the three highland Kirghiz populations of Pamir and Tien-Shan. However, comparative analysis of highland and steppe Mongoloids revealed significant differences in the following variables: (1) mean number of Q variants per individual, 2.50 and 3.49 in the highland and steppe populations, respectively; (2) frequency of Q variants in 7 of the 12 autosomes studied; and (3) distribution of homo- and heteromorphs in four autosomal pairs (13-15, 21), with a preponderance of individuals with increased hemomorph (-/-) frequency in highlanders. The following questions are discussed: (1) the possible selective value of chromosomal Q-heterochromatin material in the adaptation of human populations to extreme environmental factors, in particular to the high-altitude environment of Pamir and Tien-Shan; (2) the existence of intraracial heterogeneity in Mongoloids living in different ecological zones; and (3) the possible taxonomic value of Q-variant inversion in chromosome 3.
Chromosomal Q polymorphism was studied in 157 adolescents of Yakut nationality (67 males and 90 females) living in Eastern Siberia, on the territory of the Yakut ASSR. Of the 157 subjects, 123 had chromosomal Q variants while 34 (21.7%) had no Q-heterochromatin bands with fluorescence levels 4 and 5. The mean number of Q variants per individual ranged from 0 to 5, with a mean of 1.64. No differences were observed in the frequency of Q variants between sexes. The observed homo- and heteromorph frequencies always agreed with those predicted by the law of Hardy-Weinberg. Of the 157 subjects, four (2.55%) had pericentric inversion of the Q-heterochromatin band in chromosome 3. The following topics are discussed: possible selective value of chromosomal Q-heterochromatin material in the adaptation of human populations to extreme environmental factors, in particular to cold; the taxonomic value of chromosomal Q polymorphism in ethnic anthropology.
Chromosomal Q polymorphism was studied in 200 Russian individuals (94 females and 106 males) living in Kirghizia. Of the 200 individuals, 191 had chromosomal Q polymorphic variants, while nine (4.5%) had no Q bands with fluorescence levels 4 and 5. The mean number of Q variants per individual ranged from 0 to 7, with a mean of 2.9. There were no differences in the frequency of Q variants between sexes. The observed homo- and heteromorphic frequencies completely agreed with those predicted by the law of Hardy-Weinberg. Of the 200 individuals, 12 (6.0%) had pericentric inversion of the Q band in chromosome 3, one individual (0.5%) having a homomorphic form of this inversion. The possible selective value of chromosomal Q heterochromatin material in the adaptation of human populations to extreme environmental factors, in particular to cold, and the possible taxonomic value of inverted Q heterochromatin bands in chromosome 3 in ethnic anthropology, are discussed.
We studied the polymorphisms of HLA-DR and HLA-DQ products from HLA-DRw13 haplotypes by analyzing the restriction of influenza A-specific cloned T cells from an HLA-DRw13,DQw1,Dw19 homozygous individual. The results show that some functional epitopes, which can be borne by either HLA-DR or HLA-DQ molecules, are strictly correlated with the HLA-Dw19 subtype of HLA-DRw13. This clearly indicates that both HLA-DR and HLA-DQ products contribute to the HLA-Dw19 subdivision of HLA-DRw13. At least two different restricting epitopes are borne by DR products: one is correlated with the HLA-DRw13 serologically defined specificity, which includes Dw19 and Dw18 haplotypes; the other is correlated with the only HLA-Dw19 subtype of HLA-DRw13. Restricting epitopes borne by DQ molecules have been found on Dw19 cells only. DQ-restricted clones were unable to react with DQw1 APC of any other haplotypes tested, including DR1, DR2-long, DR2-short, and DRw14, demonstrating a high degree of functional polymorphism among the serologically defined DQw1 specificities.
In our study we searched for an association between the insertion/deletion (I/D) polymorphism at the ACE locus as well as apo A-I promoter polymorphism and coronary artery disease (CAD) in patients with familial hypercholesterolemia (FH). 34 FH patients over 40 years were ascertained; 16 patients with CAD were compared with 18 patients without CAD. There was an excess of DD or ID genotype in FH patients with CAD (OR = 4.9, CI = 1.17-22.17; Fisher exact p = 0.012), however, no association between G to A substitution in the promoter region of the apo A-I gene and CAD was found. Our results suggest that the DD/ID genotype at the ACE gene locus might be an important genetic risk factor for CAD in FH patients.
The immunoreactivity of apolipoprotein B (apo B) in plasma samples obtained from a variety of subjects was analysed by non-competitive ELISA with a polyclonal and a monoclonal (BIP 45) anti-LDL antibody. Three populations were tested: the first, comprising 244 healthy male volunteers, provided reference values; the second consisted of a population undergoing coronary angiography (n = 88) and was divided into a subgroup with (n = 64) and without (n = 24) coronary artery disease (CAD); the third was made up of 56 patients with heterozygous familial hypercholesterolemia. Total apo B (measured with the polyclonal antibody) was increased in the populations with CAD and in the heterozygous familial hypercholesterolemic subjects compared to the reference population. When monoclonal antibody BIP 45 was used in the non-competitive ELISA, three different patterns emerged in each population, corresponding to weak, intermediate and strong binding of the particles containing apo B to the monoclonal antibody. This may result from genetic polymorphism of apo B, and in the reference population the data fit a model consisting of two co-dominant apo B alleles (BIP(-) and BIP(+]; the 3 subpopulations then correspond to the 2 homozygotes and the heterozygote. The number of patients whose particles bound weakly to monoclonal BIP 45 antibody was low in the CAD population, while intermediate binding was increased in this group. Nevertheless, when the analysis of variance of allele BIP(-) was studied no significant difference between groups was established. This finding indicates that the genetic difference in apo B detected by BIP 45 may not be significant in the development of CAD. Furthermore, the apo B genetic polymorphism detected by BIP 45 is not associated with a particular lipoprotein level in the reference population.
Type I (insulin-dependent) diabetes in humans is characterized by a T cell mediated destruction of insulin-secreting pancreatic beta cells. This autoimmune response is very similar to that seen in the non-obese diabetic (NOD) mouse strain. Originally bred from the ICR cataract-prone strain, NOD mice spontaneously develop T cell mediated insulitis and type I diabetes by the age of 6 months. Backcross studies with the NOD mouse strain indicate segregation of at least three recessive genes. One of these, Iddm-1, has been shown to be tightly linked to the mouse MHC, H-2 on chromosome 17. Comparative studies with diabetic patients has also shown linkage to human HLA with protective and predisposing haplotypes being present within the population. In this study we have attempted to identify restriction fragment length polymorphisms (RFLPs) between the genomes of the NOD mouse strain and the diabetes-resistant strain C57BL/10. Such polymorphic loci will be used to screen DNAs from backcross animals that are diagnosed diabetic in an attempt to identify probes linked to the non-H2 disease susceptibility genes.
Overexpression of cathepsin D in human breast cancers is associated with a higher risk of relapse and metastasis. Also, pro-enzyme routing is altered in several tumoral mammary cell lines, leading to its hypersecretion. MCF7 cells compared to normal kidney carry a C-->T transition at position 224 in the cathepsin D gene which converts Ala to valine in its pro-fragment. Using polymerase chain reaction-single strand conformational polymorphism analysis (PCR-SSCP), the variant T allele frequency was found to be 23-30%, and equally distributed in cancer and normal cells. Six to nine per cent of genotypes were homozygous T/T, 34-41% were heterozygous T/C and 50-59% were homozygous C/C. Moreover, genotypes were identical in 19 out of 20 matched sets of tumoral mammary cells and normal white blood cells from the same patients. Loss of heterozygosity was noted in 1 case. C/T224 transition is thus not due to a somatic event. However, this missense polymorphism might modify procathepsin D secretion and/or maturation in breast cancer cells.
BACKGROUND: Hereditary polymorphic light eruption (HPLE) occurs unique ly in the American Indian and Inuit and exhibits autosomal dominant transmission. Because the cutaneous expression of HPLE resembles that of polymorphic light eruption (PLE) and because many non-Indians in the United States have American Indian heritage, some instances of PLE may actually be HPLE. OBJECTIVE: Our purpose was to determine whether non-Indian patients with PLE have characteristics suggestive of HPLE. METHODS: We surveyed in Nebraska 25 European-Caucasian and 36 African-American patients with PLE for American Indian heritage and photosensitive relatives. Nonphotosensitive subjects (52 Caucasians and 40 African Americans) were surveyed for American Indian heritage. RESULTS: American Indian heritage occurred in 11 Caucasian patients (44%); of those, seven (64%) had photosensitive relatives. Likewise, 29 African Americans (81%) had American Indian heritage; 19 (66%) of those had photosensitive relatives. American Indian heritage occurred in 10 Caucasian control subjects (19%) and in 34 African-American control subjects (85%). CONCLUSION: If American Indian heritage and a family history of photosensitivity are definitive for HPLE, seven (28%) of our Caucasian patients and 19 (53%) of our African-American patients have HPLE rather than PLE. We urge physicians who suspect PLE in non-Indians to ask about American Indian heritage and photosensitive relatives and to screen their present patients with PLE for such characteristics.
Data on enzyme polymorphism and blood group polymorphism were examined with special reference to molecular evolution, by using a statistic that depends on neither population structure nor other ecological factors. The data of the former are consistent with the hypothesis of neutral mutant and random genetic drift, whereas the latter are in accord with the hypothesis of balanced selection.