The A1 allele of TaqI A restriction fragment length polymorphism (RFLP) in the D2 receptor (DRD2) gene locus has been suggested to be associated with low D2 receptor density in man. Striatal dopamine transporter (DAT) densities were studied with [(123)I]2-beta-carbometoxy-3beta(4-iodophenyl)tropane and single-photon emission tomography in 29 detoxified alcoholics, who were also genotyped for the two alleles of TaqI A RFLP at the DRD2 receptor gene locus. Alcoholics with the A1/A2 genotypes (n = 10) had statistically significantly higher DAT densities than subjects with the A2/A2 genotypes [n = 19; 8.0 +/- 1.2 (mean +/- SD) vs 6.9 +/- 1.1, P = 0.035]. We suggest that the TaqI A RFLP is in linkage disequilibrium with a gene variant modifying DAT density in alcoholics.
Large multifunctional protease LMP2 (Arg60-->His), LMP7 (Lys145-->Gln) and PSMA6 (C(-8)-->G) gene allelic polymorphisms in 147 young patients with essential hypertension and in 208 practically healthy people were determinated. It was shown that interrelation of genotypes Arg/Arg, Arg/His and His/His in LMP2 gene polymorphisms account 42.5 %, 46.4% and 11.1% correspondingly (in control--63.9%, 28.6%, 7.5%; P = 0.001 by c2-test). Allelic variants of PSMA6 dispense the next manner: C/C--76.2%, C/G--21.1%, G/G--2.7% in adolescents with EH (in control--69.8%, 29.7% and 0.5% correspondingly, P = 0,047). Analysis of LMP7 gene polymorphism showed identical frequency of different genotypes in patients (Lys/Lys--92.4%, Lys/Gln--7.6%, Gln/Gln--0%) and practically healthy people (97.3%, 2.7%, 0% correspondingly; P = 0.16). Obtained data suggest the LMP2 and PSMA6 gene polymorphisms significance as the risk factors of essential hypertension in adolescents.
The results of DNA analysis of deletion in exons 7 and 8 of SMN gene, and exon 5 of NAIP gene in 24 SMA-families from Ukraine are presented. Deletions of SMN exons 7 and 8, or 7 were found in 46 (97.9%) of 47 SMA-chromosomes. A homozygous deletion of NAIP exon 5 was demonstrated in 4 (19%) of 21 SMA-families. The authors have demonstrated that in 2 SMA patients with homozygous deletion SMN exon 7 only, the remaining SMN exon 8 was a part of a chimeric CBCD41/SMN gene.
We developed a suitable method for analysing dinucleotide repeats found in the upstream of human alpha-estrogen receptor (ER) gene by applying capillary electrophoresis and automatic analysis. This method omits the gel-casting step as well as difficult handling of long polyacrylamide sequencing gels. Use of radioactive materials is also avoided. Using this method, the frequency distribution of ER alleles, determined in 180 Finnish individuals showed two peaks at 12 and 14 repeats (166 and 168 bp) and also at 22 and 24 repeats (184 and 186 bp). The overall distribution of alleles seemed to be similar to that found among Italian and Japanese populations.
The object of the investigation reported in this paper was to study, from the point of view of statistical and geometric theory of pattern recognition, the DNA optical density distribution peculiarities in the interphase nuclei of buccal epithelium present in the pathology of the thyroid and mammary glands. Two new indices to characterize this distribution (ratio of modal class volumes and relief index) are proposed. It is shown that in malignant neoplasms of the thyroid and mammary glands the changes in the nuclei of buccal epithelium are characterized by an increase in the optical density of DNA over a range from 0.15 to 0.30 in conventional units of measure, as compared with its values in benign pathological processes. The sensitivity of the proposed criterion for diseases of the thyroid gland is equal to 76.2% and the specificity is equal to 85.8%. For diseases of the mammary gland (excluding IDLC) we have discovered that the sensitivity of the method is equal to 94.29% and its specificity equal to 90.91%. In diseases of the mammary gland (including IDLC) we have discovered that the sensitivity of the method is equal to 71.42% and its specificity is equal to 90.91%.
The variability of four microsatellite loci of rodents, caught from the head part of Eastern Urals Radioactive Trace (EURT), along with the rodents inhabiting contiguous zone with background radiation level and distant-reference territory, was analyzed forthe first time. Differences in the parameters of genetic diversity between northern red-backed voles from the EURT zone and from the reference population were detected. An increase in some indices of genetic diversity in animals from a contiguous to the EURT zone was found; this is probably associated with animal migration and configuration of the area of pollution. A transfer of radiation-induced effects to the contiguous territories and a decrease in the possibility of fixation of adaptations in a series of generations of mobile rodent species in the area of local radioactive pollution are consequences of migrations. The results of the study make it possible to recommend microsatellite markers for the analysis of radiation-induced effects in rodents as model objects of radioecological monitoring.
The EcoR1 polymorphism of the apolipoprotein B gene (APOB) is thought to be associated with atherothrombotic type of ischemic stroke (ATTIS) with the APOB*R1/R2 genotype as a marker of increased risk for ATTIS. We estimated odds ratio for this genotype as 2.17 in ethnic Russians and 3.39 in ethnic Tartars. The association between the EcoR1 APOB gene polymorphism and ATTIS confirmed the results of previous studies on relation of the APOB gene to vascular pathology caused by elevated lipid level and atherogenesis.
Results of analysis of chimeric SMN genes among some high SMA-risk families from Ukraine using the EcoRV and DdeI restriction enzyme hydrolysis of PCR products is presented. Chimeric cen/telSMN gene was detected in probands with homozygous deletions of telSMN exon 7 only, as well in proband with absent of homozygous deletion of exons 7 and/or 8 of the SMN gene. Effectivity of approach of detection of chimeric SMN genes based on the EcoRV and DdeI restriction enzyme analysis of PCR products and mechanisms of formation of chimeric SMN genes are discussed.
[An analysis of mutations in the 7th, 10th and 11th exons and of the polymorphism of the 4 nucleotide tandem repeats from the 3' end of the 6th intron of the CFTR gene in families from Ukraine with a high risk of mucoviscidosis]
Mutations in the CFTR gene have been screened in 110 families from Ukraine with high risk of cystic fibrosis. Deletion F508 was found in 121 (55%) of 220 CF alleles. Among the rest mutant alleles (with the absence of delta F508) six other mutations occurring in the 7th, 10th, 11th exons of the CFTR gene were screened. In this way, 5 CF alleles may be characterized: 1 allele with R334W (the 7th exon) 1 with 1677 delTa (the 10th exon), 1 allele with G551D and 2 alleles with R553X (the 11th exon). We have screened 865 healthy donors for F508 from different regions of Ukraine. The frequency of heterozygous carriers in different regions ranged from 1:28 to 1:170. Strong linkage imbalance was found between polymorphic markers of 4 bp tandem repeats from the 3'-end of the sixth intron in the CFTR gene and deletion F508.
The causes of the late Pleistocene megafaunal extinctions are poorly understood. Different lines of evidence point to climate change, the arrival of humans, or a combination of these events as the trigger. Although many species went extinct, others, such as caribou and bison, survived to the present. The musk ox has an intermediate story: relatively abundant during the Pleistocene, it is now restricted to Greenland and the Arctic Archipelago. In this study, we use ancient DNA sequences, temporally unbiased summary statistics, and Bayesian analytical techniques to infer musk ox population dynamics throughout the late Pleistocene and Holocene. Our results reveal that musk ox genetic diversity was much higher during the Pleistocene than at present, and has undergone several expansions and contractions over the past 60,000 years. Northeast Siberia was of key importance, as it was the geographic origin of all samples studied and held a large diverse population until local extinction at approximately 45,000 radiocarbon years before present ((14)C YBP). Subsequently, musk ox genetic diversity reincreased at ca. 30,000 (14)C YBP, recontracted at ca. 18,000 (14)C YBP, and finally recovered in the middle Holocene. The arrival of humans into relevant areas of the musk ox range did not affect their mitochondrial diversity, and both musk ox and humans expanded into Greenland concomitantly. Thus, their population dynamics are better explained by a nonanthropogenic cause (for example, environmental change), a hypothesis supported by historic observations on the sensitivity of the species to both climatic warming and fluctuations.