Genetic studies of an apoA-I lipoprotein variant

Summary Chromosomal Q polymorphism was studied in 116 Turkmen, aboriginals of the Kara-Kum desert of Central Asia. Propylquinacrine mustard was used as fluorochrome. Of the 116 subjects aged 16–20 years, 109 (94.0%) were found to have Q-polymorphic variants, while seven (6.0%) showed complete absence of Q bands with fluorescence levels 4 and 5. There was a total of 351 polymorphic Q bands, 0–7 per individual, with a mean of 3.0 in the population. No differences between sexes were observed in the frequency of Q bands. The observed homo- and heteromorph frequencies proved to be in complete agreement with those predicted by the law of Hardy-Weinberg. Chromosome 3 with pericentric inversion of the Q-heterochromatin band was found in two (1.7%) of the 116 subjects.The following questions were examined: (1) the possible selective value of chromosomal Q-heterochromatin material in the adaptation of human populations to extreme environmental factors, in particular to the desert climate; (2) intracial heterogeneity in Europoids of Eurasia; (3) the taxonomic value of Q polymorphism in ethnic anthropology.     

Human chromosomal polymorphism. III. Chromosomal Q polymorphism in Mongoloids of northern Asia

Summary Q-heterochromatin variants in seven autosomes (3, 4, 13–15, 21, 22) were studied in two Mongoloid populations of northern Asia (Chukchi and Khakass). Q-staining was obtained using propylquinacrine mustard. Of 132 Chukchi individuals aged 13 to 20 years, 124 had Q-polymorphic chromosomes, while eight (6.0%) had no bands with fluorescence levels 4 and 5. The mean number of Q variants was 2.2 per individual.Of the 120 Khakass individuals aged 14 to 17 years, 112 had Q-polymorphic chromosomes, while eight (6.7%) had no Q variants with fluorescence levels 4 and 5. The mean number of Q variants was 2.5 per individual. No differences were found in the frequency of Q variants between sexes in the two populations. There was complete agreement between the observed homo-and heteromorphic frequencies and those predicted by the law of Hardy-Weinberg. As the Mongoloid populations of northern Asia showed statistically significant homogeneity both in the frequency of Q variants and the distribution of homo-and heteromorphic variants, they were examined as a single group—that of northern Mongoloids. The following questions are discussed: (1) the possible selective value of chromosomal Q-heterochromatin material in the adaptation of human populations to certain extreme environmental factors, in particular to cold and hypoxia; (2) the intraracial heterogeneity of Asian Mongoloids; (3) the taxonomic value of chromosomal Q polymorphism in ethnic anthropology.     

Human chromosomal polymorphism. IV. Chromosomal Q polymorphism in Russians living in Kirghizia

Summary 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.     

Human chromosomal polymorphism. V. Chromosomal Q polymorphism in African populations

Summary The distribution pattern of Q-heterochromatin variants in seven autosomes (3, 4, 13–15, 21, and 22) was studied in three aboriginal Negroid populations of Africa (Mozambique, Angola, and Ethiopia). It was shown that among African Negroids there are no individuals completely lacking Q-heterochromatin bands with fluorescence levels 4 and 5. The mean number of Q variants per individual was 3.47, 4.80, and 4.85 in the Ethiopian, Mozambique, and Angola populations, respectively. The observed homo- and heteromorphic frequencies always agreed with those predicted by the law of Hardy-Weinberg. The populations of tropical lowland Negroids (Mozambique and Angola) proved to be significantly homogeneous both in the frequency of Q variants and the mean number of these variants per individual, so they were examined as a single group. However, comparative analysis of highland (Ethiopians) and lowland Negroids revealed statistically significant differences. The following questions are discussed: (1) the possible selective value of chromosomal Q heterochromatin material in the adaptation of human populations to high-altitude climate; (2) the possible existence of intraracial heterogeneity in Negroids living in different ecological zones of Africa; (3) the possible taxonomic value of an inverted Q-heterochromatin band in chromosome 3 in ethnic anthropology.     

Human chromosomal polymorphism. VII. The distribution of chromosomal Q-polymorphic bands in different human populations

The distribution of chromosomal Q-polymorphic bands was studied in different human populations. The populations studied showed no differences in the relative amount of Q bands in all the 12 polymorphic loci of seven autosomes, but interpopulation differences did exist in the absolute amount of Q bands in all the 12 potentially polymorphic loci of seven autosomes, these differences consisting of uniform increases or decreases in this absolute amount. Comparisons of the mean number of Q-heterochromatin bands with fluorescence levels 4 and 5 per individual showed a consistent prevalence of this quantitative parameter of chromosomal Q polymorphism in females as compared to males in all the national groups. It is suggested that there is some dosage compensation of chromosomal Q-heterochromatin material in females due to the absence of a chromosome in their genome, which is able to "compensate" for the large Q band in chromosome Y which is present only in the karyotype of males.     

Human chromosomal polymorphism

Chromosomal Q-polymorphism was studied in 198 Kirghiz subjects (98 males and 100 females) from one high-altitude isolate located in the south-eastern part of Kirghizia. Small samples of mountaineers (N = 37) and volunteer subjects (N = 34) were also studied. The samples studied did not differ significantly from each other in the relative frequencies of chromosomal variants in 12 loci of seven Q-polymorphic autosomes. The mean number of Q variants per individual in the populations ranged from 1.3 to 2.0. No sex differences were found in the frequencies of Q variants. The observed homo- and heteromorphic frequencies agreed with those predicted by the law of Hardy-Weinberg. The possible selective value of chromosomal Q heterochromatin material in the adaptation of human populations to high-altitude climate is discussed.     

Human chromosomal polymorphism. I. Chromosomal Q polymorphism in Mongoloid populations of central Asia

Summary 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 homomorph (-/-) 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.     

The relationship between the Y chromosome size and the amount of autosomal Q-heterochromatin in human populations

The relationship between the basic quantitative characteristics of the Q-heterochromatin (Q-HR) region variability of autosomes and of the Y chromosome in human populations was examined. A definite relationship between the mean number of Q-HR per individual, the distribution and frequencies of Q-HR on autosomes and the size of the Q-heterochromatin segment of the Y chromosome at the population level was shown to exist. The amount of autosomal Q-HR was lower in individuals with larger Q-heterochromatin segments on Y chromosomes, and vice versa. The hypothesis that the amount of chromosomal Q-HR in the genome of modern human populations may be under the control of natural selection, is discussed.     

Chromosomal Q-heterochromatin regions in native highlanders of Pamir and Tien-Shan and in newcomers

The variability of human chromosomal Q-heterochromatin regions (Q-HR) was studied in 385 newcomers well adapted to the extreme environmental conditions of Pamir and Tien-Shan, as well as in 284 representatives of the native population of these regions. Newcomers were found to represent a highly homogeneous group as regards all the quantitative characteristics of Q-HR variability, but at the same time they differed significantly from both native residents and individuals of similar nationality (Russians) living permanently at low altitude. Differences between these three groups in the amount of Q-HRs in their genome are discussed as evidence in favour of the hypothesis of the possible selective value of chromosomal Q-heterochromatin material in human adaptation to extreme environmental high-altitude conditions.     

Human Q and C chromosomal variations: distribution and incidence.

Chromosome preparations of 77 normal newborn babies from Grand Junction, Colorado, were stained first for G-band identification of each chromosome and subsequently stained for Q- and C-band localization. This approach permitted determination of the variation of the C region size in all chromosomes, and is the first such study reported. A total of 391 Q and C variants was described, an average of 5.08 +/- 0.23 per subject; 225 were Q varients, 166 were C variants. Q varients were distributed among seven chromosomes in the genome and among 76 of the 77 subjects. Chromosomes 3 and 4 had variable Q intensities at the centromere, and the acrocentric chromosomes, 13, 14, 15, 21, and 22, had variable Q intensities in their short arms and/or satellites. C variants, though fewer in number, were more widely distributed in the genome, with at least one variant described in each chromosome. C variants were identified in 65 of the 77 subjects. Most unique were the six pericentric inversions found in chromosome 9. Except for giant satellites, no correlations were found between Q and C variants. Q and C variants evaluated in 16 members of four families showed that in nearly every case each variant observed in a child could be demonstrated in one or both parents. It is evident from this study that the magnitude of chromosomal variation in human populations is far greater than heretofore believed. It has also been shown that the combination of Q- and C-banding procedures will yield much more information than either technique used alone and is therefore the preferred approach to many population and gene localization studies.     

Cytogenetic investigations in 150 cases with complaints of sterility or primary amenorrhea

Summary Cytogenetic investigations were carried out on 150 individuals. Out of these 107 were females and 43 males. Eighty seven of the above (43 males and 44 females) had been referred for sterility. Sixty three patients had primary amenorrhea and had been referred directly to this laboratory by clinicians, having been suspected of genetic abnormalities. Twenty-two cases (14.7%) involved in this study showed chromosomal abnormalities and seven cases (4.7%) showed chromosomal polymorphism. Of the 107 females (44 sterile and 63 with primary amenorrhea), 11 (10.2%) showed numerical or structural sex chromosomal abnormalities. Five patients (4.67%) showed chromosomal polymorphism involving the paracentromeric and centromeric regions of chromosomes 1 and 9, double satellites, and giant satellites. Of the 43 males, 11 (25.59%) showed numerical and structural abnormalities. Ten cases were anomalies involving the sex chromosomes. One case of a triple autosomal translocation in an otherwise phenotypically normal azoospermic male was of particular interest. Two cases (4.65%) showed double satellites of the acrocentrics.     

Start codon targeted polymorphism for evaluation of functional genetic variation and relationships in cultivated peanut (<Emphasis Type="Italic">Arachis</Emphasis><Emphasis Type="Italic">hypogaea</Emphasis> L.) genotypes

Cultivated peanut possesses an extremely narrow genetic basis. Polymorphism is considerably difficult to identify with the use of conventional biochemical and molecular tools. For the purpose of obtaining considerable DNA polymorphisms and fingerprinting cultivated peanut genotypes in a convenient manner, start codon targeted polymorphism technique was used to study genetic diversity and relatedness among 20 accessions of four major botanical varieties of peanut. Of 36 primers screened, 18 primers could produce unambiguous and reproducible bands. All 18 primers generated a total of 157 fragments, with a mean of 8.72 ranging from 4 to 17 per primer. Of 157 bands, 60 (38.22%) were polymorphic. One to seven polymorphic bands were amplified per primer, with 3.33 polymorphic bands on average. Polymorphism per primer ranged from 14.29 to 66.67%, with an average of 36.76%. The results revealed that not all accessions of the same variety were grouped together and high genetic similarity was detected among the tested genotypes based on cluster analysis and genetic distance analysis, respectively. Further, accession-specific markers were observed in several accessions. All these results demonstrated the following: (1) start codon targeted polymorphism technique can be utilized to identify DNA polymorphisms and fingerprint cultivars in domesticated peanut, and (2) it possesses considerable potential for studying genetic diversity and relationships among peanut accessions.     

Chromosomal Q-heterochromatin regions in the indigenous population of the northern part of West Siberia and in new migrants

The variability of Q-heterochromatin regions (Q-HR) was studied in native residents of the northern part of West Siberia, viz Yakuts (n = 127), Selkups (n = 90) and Khants (n = 54), as well as in newcomers including oil-borers (n = 43) and children (n = 113) living permanently in this part of the USSR. The major quantitative characteristics of chromosomal Q-HR variability were shown to be very similar in oil-borers and natives, and this is considered to be the result of specific selection of individuals according to the amount of Q-HRs in their genome. The hypothesis on the possible selective value of chromosomal Q-HRs in human adaptation to extreme environmental conditions of the extreme north is discussed.     

The K121Q polymorphism of the plasma cell glycoprotein-1 gene is not associated with diabetes mellitus type 2 in German Caucasians.

The K121Q polymorphism of the human plasma cell membrane glycoprotein 1 (PC-1) gene is known to be associated with diabetes mellitus type 2 in some populations studied, with contradictory results. The purpose of the present study was to examine a possible association between the presence of diabetes and the PC-1 K121Q polymorphism in a German Caucasian population. Associations between the polymorphism and various metabolic and anthropometric parameters were also examined. The presence of the K121Q variant was investigated using polymerase chain reaction restriction fragment-length polymorphism in 402 subjects with diabetes (231 men, 171 women, age 63+/-11 yrs, body mass index 28.7+/-5.1 kg/m2) and in 432 age- and sex-matched controls (247 men, 185 women, age 64+/-7 yrs, BMI 26.5+/-3.7 kg/m2). Ninety-seven subjects were carriers of the K121Q polymorphism in the control and 110 in the diabetic group (allelic frequency 11.9% and 14.7%, respectively, P=0.25). The polymorphism had no significant influence on the presence of atherosclerotic disease, body mass index, and blood pressure, both, in diabetics and in non-diabetic controls. Our data suggest that the K121Q polymorphism of the PC-1 gene is not associated with diabetes, obesity, hypertension or atherosclerosis in a German Caucasian population.     

The origin of modern humans: A cytogenetic model

A new model of the origin of man is proposed on the basis of recent studies on cytogenetics of chromosomal Q-heterochromatin regions (Q-HRs) in man and other higher primates. This model is based on the following facts: a) chromosomal Q-HRs were found in the genome of only three higher primates (man, the chimpanzee and the gorilla); b) chromosomal Q-HRs in the human genome, unlike those in apes, exhibit considerable quantitative variability; c) the number of human chromosomal Q-HRs in the genome has a selective value in the adaptation of human populations to various environmental conditions. According to this model, the three major morphofunctional distinctions of man—great physiological flexibility, characteristic morphological structure, and conceptual thinking—arose as a result of the capacity of our remote ancestors to broadly change their genome mass owing to features of chromosomal Q-HRs that are only intrinsic to man. We feel that genome-mass variability through chromosomal Q-HRs allowed man to adapt himself to various environments over such a short period of time.     

Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians

Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and −1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population. The apolipoprotein gene cluster variants were analysed in 416 angiographically determined coronary artery disease patients and matched 416 controls using polymerase chain reaction—restriction fragment length polymorphism. The characteristics of the study subjects were analyzed statistically for their association with the polymorphisms. The alleles were combined as haplotypes and their combined risks were evaluated. The minor allele genotypes of both apolipoprotein C3 (S2) and apolipoprotien A5 (C) had a significant risk for coronary artery disease. The S2 allele genotyped patients had a significantly increased triglyceride level (P < 0.001) and increased triglycerides were observed among both patient and control CC genotype carriers. We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients. We conclude that the variants on apolipoprotein C3 and apolipoprotien A5 modulate serum triglyceride levels and increase the risk of coronary artery disease.     

The ENPP1 K121Q polymorphism is not associated with type 2 diabetes and related metabolic traits in an Iranian population

The K121Q polymorphism of the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been variably associated with insulin resistance and type 2 diabetes (T2D) in several populations. However, this association has not been studied in Iranian subjects and we hypothesized that the K121Q variant might be associated with T2D and related metabolic traits in this population. The K121Q genotypes were determined by PCR-restriction fragment length polymorphism in 377 normoglycemic controls and 155 T2D patients. T2D patients had significantly higher values for systolic and diastolic blood pressure, BMI, glucose, cholesterol, triglyceride, LDL, apoB, insulin, and HOMA-IR, and lower levels of HDL than the normoglycemic subjects. The frequency of the Q allele did not differ between T2D and normoglycemic subjects (OR 0.96, 95% CI 0.90-2.00, P?=?0.70). The Q allele frequency was 16.5% in T2D and 15.2% in normoglycemic subjects. The ENPP1 genotype (KQ?+?QQ) was not associated with the systolic and diastolic blood pressure, glucose, triglyceride, cholesterol, LDL-C and HDL-C, apo B, BMI, HOMA-IR, and insulin levels in both normoglycemic and T2D groups. Our results suggest that the ENPP1 121Q allele might not be associated with T2D and related metabolic traits among Iranian subjects.     

Alleic variants of human melatonin 1a receptor: function and prevalence in subjects with circadian rhythm sleep disorders.

The human melatonin 1a (hMella) receptor gene was screened for mutations using genomic DNA samples from patients with circadian rhythm sleep disorders and control subjects by single strand conformational polymorphism analysis (SSCP). We found seven mutations, two of which predict amino acid changes R54W and A157V, respectively. The prevalence of the R54W variant and that of the A157V variant were several times more common in non-24-h sleep-wake syndrome subjects than among control subjects, although the incidence was not significant in our study group. When expressed in COS-7 cells, the R54W mutant receptor exhibited significantly reduced B(max) and slightly enhanced affinity (reduced K(d)) compared to the wild type receptor, while the A157V variant receptor showed similar binding characteristics to the wild type. The identification of variants in the hMella receptor will provide a useful tool for analyzing genetic predisposition toward various diseases related to melatonin function and to clarify the physiological role of melatonin receptors in humans.     

Polymorphism of the fourth component of complement in Turks

An analysis of polymorphism in the fourth component of human complement (C4) was performed on EDTA-plasma from 142 unrelated, randomly selected Turks without collagen-vascular disease or recurrent infections. Plasma samples treated with neuraminidase and carboxypeptidase-B were subjected to high-voltage agarose gel electrophoresis followed by immunofixation. C4B allotypes were further detected in some samples by Western blots with monoclonal antibody 1228 (anti-C4B/Ch1 reactivity). The frequencies of C4A and C4B alleles were determined. Allele C4B*5, which has been found to be relatively common in Asian (Oriental) populations, was not detected in this study. No specific predilection could be noted among the rare variants. C4A*3-C4B*1 was the most common haplotype (n = 40/142, or 28%) but was found less frequently than in Caucasian populations. This finding may be the result of the limited number of samples examined. C4A and/or C4B null allotypes were seen in 49 of 142 (34.6%) subjects. The most frequent C4 null allotype seen was C4B null (37/142, or 26%): 28 subjects had one C4B null allele; 1 had a homozygous deficiency of C4B (C4B*QO, *QO) and 7 had C4A*QO C4B*QO, a double heterozygous haplotype. Frequencies of homozygous haplotype C4A*Q0-C4B*Q0 in the population studied were found to be 0.007. The results of this study demonstrate that the genetic composition of the Turkish population exhibits both similarities and differences with the European population, and ranges between Caucasian and Mongoloid (Asian) populations.     

Chromosomes. Aging. Longevity

Investigations dealing with the characteristics of chromosomal apparatus at late stages of ontogenesis are analyzed. Both structural and functional changes in the chromosomal apparatus are observed in ageing. Some papers indicate to the association of certain variants of chromosomal polymorphism with the longevity "phenomenon".