Angiotensin II type 1 receptor gene polymorphism and telomere shortening in essential hypertension

Several genetic studies were carried out among hypertensive patients to assess allelic association at the 1166 position of the 3' untranslated region of angiotensin II type 1 receptor gene. In addition, attempts have also been made to find out whether telomere length attrition is associated with hypertension. The main aim of this study was to examine the association of A1166C polymorphism of angiotensin II type 1 receptor and telomere length with essential hypertension in Egyptian people. Angiotensin II type 1 genotyping and relative telomere length were investigated by PCR in 40 patients of essential hypertension and 15 healthy controls. The homozygous AA1166 allele frequency was 92.8% among the studied subjects. There was no intergroup variation in A allele frequency in normotensive group. The frequency of homozygous A allele was significantly higher in hypertensive than normotensive subjects (97.5 and 80%, respectively) with higher frequencies in male patients. The average telomere length ratio was significantly shorter in hypertensive than in normal subjects (1.08?±?0.3 and 1.54?±?0.18, respectively). No correlation was observed between telomere length ratio and body mass index. This study suggests that the homozygous A1166 allele of angiotensin II type 1 and short telomeres may be predisposing factors for essential hypertension in Egyptians and may be involved in the pathogenesis of the disease. Further strategies for treating high-risk patients could result in prevention or delay of end organ damage.     

Increased frequency of the S-allele of the L-myc oncogene in breast cancer

BACKGROUND: Association between restriction fragment length polymorphisms (RFLP) of known oncogenes and a predisposition to develop cancer have been postulated. The L-myc gene is a potential molecular marker associated with cancer susceptibility as well as metastasis, prognosis, and adverse survival. Our aim was to test the hypothesis that there was an association between L-myc S allele in breast cancer and a predisposition to the disease. MATERIALS AND METHODS: The distribution of L-myc polymorphism in 56 patients with breast cancer was determined by polymerase chain reaction-based restriction fragment length polymorphism and compared with that of 51 healthy control subjects. RESULTS: The allele frequencies of L and S in breast cancer patients were 0.70 and 0.30, respectively and those in normal individuals were 0.54 and 0.46, respectively. This difference was primarily the result of a high frequency of the S allele among breast cancer patients compared to controls. The frequency of S allele was significantly higher in breast cancer patients than in normal individuals (p < 0.01). No correlation was observed between the presence of L-myc S allele and several parameters of each patient's history or characteristics of tumor. CONCLUSION: Our results suggested that L-myc polymorphism may be significant in an individual's susceptibility to breast cancer in Turkey and may be useful for identifying patients at high risk of developing breast cancer.     

BsmI polymorphisms in vitamin D receptor gene are associated with diabetic nephropathy in type 2 diabetes in the Han Chinese population

We investigated the relationship between BsmI/ApaI polymorphisms in vitamin D receptor gene and diabetic nephropathy in a Han Chinese population. PCR-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI and ApaI polymorphisms in 304 patients with type 2 diabetes mellitus (DM group) and 100 control individuals (ND group). The DM group was further divided into DN0 (no diabetic nephropathy), DN1 (diabetes with small amount of albuminuria), DN2 (diabetes with large amount of albuminuria), L/NDN (late-onset DN after 5 years/no DN over the whole follow-up period of 5 years) and EDN (early-onset diabetic nephropathy occurring within first year) subgroup. We found that (1) genotype and allele frequency of BsmI polymorphism had significant difference between DM and ND group; BB+Bb genotype and B allele frequency were significantly higher in DN2 group than in ND and DN0 group; the ApaI polymorphism and allele frequency did not show any difference between DM and ND group; (2) BsmI BB+Bb genotype and B allele frequency were significantly higher in EDN group than in L/NDN group; (3) among patients with nephropathy, albumin excretion rate (AER) in 24-hour urine was significantly higher in those with BB+Bb phenotype than in those with bb phenotype (P<0.01), (4) unconditional logistic regression analysis showed that BsmI BB+Bb genotype was not only correlated with type 2 diabetic nephropathy, but also correlated with early-onset type 2 diabetic nephropathy. We conclude that the allele B (BB or Bb genotype) in vitamin D receptor gene is correlated with large amount albuminuria in the Han Chinese population with type 2 diabetes, and is probably a risk factor for early-onset diabetic nephropathy.     

DNA polymorphisms of the insulin receptor gene in Japanese subjects with non-insulin-dependent diabetes mellitus

Genotypes identified by two restriction fragment length polymorphisms (RFLPs) of the insulin receptor gene (IRG) with the restriction endonuclease Sst-1 were determined in a Japanese group comprising 51 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 50 control subjects. Southern hybridization using a probe for the beta subunit of the human IRG identifies 4 alleles, termed S1(+) (5.3 kb), S1(-) (5.8 kb), S2(+) (7.0 and 2.4 kb) and S2(-) (9.4 kb). The frequencies of genotypes possessing the S1(-) allele in Japanese controls and Japanese NIDDM patients were 0.11 and 0.16, respectively. Unlike the previously reported association of the S1(-) allele with NIDDM found in Caucasians there was no significant difference in the frequency of the S1(-) allele between non-diabetic and NIDDM Japanese patients. There was a significant difference in the frequency of the S2(+) allele between Caucasian control subjects (0.14) and Japanese controls (0.0) and NIDDM patients (0.02).     

A new PstI restriction fragment length polymorphism (RFLP) of placental alkaline phosphatase. RFLP haplotypes and correlation with electrophoretic types.

A new PstI restriction fragment length polymorphism (RFLP) of placental alkaline phosphatase (PLAP) was discovered in a study of a Finnish population sample and designated PstI(b)1 or Pst(b)2 depending on the presence or absence of the cleavage site. The frequency of the PstI(b)2 allele was 0.24. This allele showed a positive (p = 3 x 10(-6) association with the electrophoretic allele 2(F) and a negative association (2 x 10(-7) with the electrophoretic allele 1(S). The previously described PstI RFLP [PstI(a)] was also found to be associated with electrophoretic types; the PstI(a)1 allele (presence of site) was associated with the electrophoretic type 2 (p = 0.023). Haplotype frequencies and disequilibria were calculated between PstI(a), PstI(b) and RsaI RFLPs. A complete disequilibrium (p = 1 x 10(-6) was found between PstI(a) and RsaI, whereas there was no significant disequilibrium between PstI(b) and RsaI. There was no strict correlation between the distances between the RFLP loci and the degree of linkage disequilibrium. The allele controlling the electrophoretic variant PLAP 18 (D) was found in polymorphic frequency (0.024) in the Finnish population.     

Polymorphic restriction sites of type II collagen gene: their location and frequencies in the Finnish population

Restriction fragment length polymorphism (RFLP) of the cartilage-specific type II collagen gene has been studied in the Finnish population. Two high-frequency alleles, also reported in other populations, were detected. The HindIII allele had a frequency of 0.33, and that detected with PvuII a frequency of 0.46. Both of these frequencies resembled the ones reported for other populations. Also one BamHI allele, not earlier reported, was found at a low frequency. Two other previously reported polymorphisms for BamHI and EcoRI were not detected in the Finnish population. The RFLPs showed a fair agreement with the Hardy-Weinberg equilibrium. A linkage disequilibrium was found between PvuII and HindIII markers. The alpha 1(II) collagen gene seems to be more conserved in populations of various origins than the alpha 2(I) collagen gene. These polymorphic collagen markers would be useful in linkage studies of various inherited cartilage disorders.     

Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P450IA1 gene.

A good correlation was observed between enhanced lung cancer risk and restriction fragment length polymorphisms (RFLPs) of the P450IA1 gene with the restriction enzyme MspI. Genotype frequencies of 0.49 for the predominant homozygote, 0.40 for the heterozygote, and 0.11 for the homozygous rare allele were observed in a healthy population. Among lung cancer patients, the frequency of homozygous rare allele of P450IA1 gene was found to be about 3-fold higher than that among healthy population, and this difference was statistically significant. This is the first report to identify the genetically high risk individuals to lung cancer at the gene level.     

新疆维吾尔族、汉族阿尔茨海默病Neprilysin基因单核苷酸多态性研究

摘要目的：探讨新疆地区维吾尔族、汉族脑啡肽酶（Neprilysin,NEP）基因单核苷酸多态性与阿尔茨海默病（Alzheimer’SdiseaseAD）的关系。方法：对新疆地区维吾尔族、汉族≥50岁8284名人群进行AD流行病学调查,参照ADRDA．NINCDS的标准,选取散发性阿尔茨海默病（sporadicAlzheimer’s disease,SAD）患者209例（AD组）与正常对照220例（对照组）,应用聚合酶链反应一限制性片段长度多态性技术（PCR）检测NEP基因多态性,采用病例一对照的关联分析方法对NEP基因rs3736187位点进行基因型和等位基因频率分析。结果：（1）新疆维吾尔族、汉族两民族AD组与对照组间NEP基因基因型频率和等位基因频率分布差异均有统计学意义（P〈0．05）。携带T等位基因个体出现AD的危险性高于携带c等位基因的个体（0R=1．981,P〈0．05）。（2）新疆维吾尔族、汉族不同民族之间比较NEP基因基因型频率和等位基因频率分布差异均无统计学意义（P〉0．05）,而在同一民族中AD组和对照组之间比较NEP基因等位基因频率分布差异均具有统计学意义（P〈0．05）。（3）两个年龄分段（〈65岁及≥65岁）之间NEP基因基因型频率和等位基因频率分布差异均无统计学意义（P〉0．05）,而在同一年龄段内部AD组与对照组间等位基因频率分布差异具有统计学意义（P〈0．05）。（4）男性、女性之间NEP基因基因型频率和等位基因频率分布差异均无统计学意义,而在女性AD组与对照组间等位基因频率分布差异有统计学意义（P〈0．05）。结论：NEP基因rs3736187位点基因型频率和等位基因频率在新疆维吾尔族、汉族两民族间的分布相似;NEP基因的T等位基因是SAD的危险因素,在新疆维吾尔族、汉族两民族及女性SAD的发病中起重要作用。     

The Characterization and Geographical Distribution of the Genes Responsible for Vernalization Requirement in Chinese Bread Wheat

The frequency and distribution of the major vernalization requirement genes and their effects on growth habits were studied.Of the 551 bread wheat genotypes tested,seven allelic combinations of the three Vrn.1 genes were found to be responsible for the spring habit,three for the facultative habit and one for the winter habit.The three Vrn-1 genes behaved additively with the dominant allele of Vrn-A1 exerting the strongest effect.The allele combinations of the facultative genotypes and the discovery of spring genotypes with "winter" allele of Vrn-1 implied the presence of as yet unidentified alleles/genes for vernalization response.The dominant alleles of the three Vrn-1 genes were found in all ten ecological regions where wheat Is cultivated in China,with Vrn-D1 as the most common allele in nine and Vrn-A1 in one.The combination of vrn-A 1vrnB 1Vrn-D1 was the predominant genotype in seven of the regions.Compared with landraces,improved varieties contain a higher proportion of the spring type.This was attributed by a higher frequency of the dominant Vrn-A1 and Vrn-B1 alleles in the latter.Correlations between Vrn-1 allelic constitutions and heading date,spike length,plant type as well as cold tolerance were established.     

Analysis of IL-1A(-889) and TNFA(-308) gene polymorphism in Brazilian patients with generalized aggressive periodontitis

Generalized aggressive periodontitis (GAP) comprises a group of periodontal diseases characterized by the rapid destruction of periodontal tissues which affect young individuals who generally present no systemic disorders. Polymorphisms in the interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) genes have been associated with an increased severity of chronic periodontitis. The objective of the present study was to evaluate the association between IL-1A (-889) and TNFA (-308) gene polymorphisms and GAP. One hundred nonsmoking subjects were selected, including 30 with GAP and 70 without periodontal disease. Gene polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. For IL-1 (-889), the frequency of genotype 1/1 was 54.3% in the control group and 56.7% in the study group. The frequency of genotype 1/2 was 37.1% in the control group and 40% in the study group. Genotype 2/2 was detected at a frequency of 8.6% and 3.3% in the control and study groups, respectively. For TNFA, genotype 1/1 was present in 68.6% of control subjects and in 80.0% of patients with GAP, while the frequency of genotype 1/2 was 27.1% in the control group and 20% in the study group. Genotype 2/2 was present in 4.3% of control subjects and was not detected in the study group. The frequencies of allele 1 and allele 2 of the IL-1A (-889) gene were 72.9% and 27.1%, respectively, in the control group and 76.7% and 23.3% in the GAP group. For the TNFA (-308) gene, the frequency of allele 1 was 82.15% in the control group and 90% in the study group, whereas the frequency of allele 2 was 17.85% in the control group and 10% in the study group. Statistical analysis revealed no significant difference in allele distribution for either gene between the two groups. No association was observed between GAP and IL-1A (-889) and TNFA (-308) gene polymorphisms in Brazilian patients.     

A latitudinal cline in the Chinook salmon (Oncorhynchus tshawytscha) Clock gene: evidence for selection on PolyQ length variants

A critical seasonal event for anadromous Chinook salmon (Oncorhynchus tshawytscha) is the time at which adults migrate from the ocean to breed in freshwater. We investigated whether allelic variation at the circadian rhythm genes, OtsClock1a and OtsClock1b, underlies genetic control of migration timing among 42 populations in North America. We identified eight length variants of the functionally important polyglutamine repeat motif (PolyQ) of OtsClock1b while OtsClock1a PolyQ was highly conserved. We found evidence of a latitudinal cline in average allele length and frequency of the two most common OtsClock1b alleles. The shorter 335 bp allele increases in frequency with decreasing latitude while the longer 359 bp allele increases in frequency at higher latitudes. Comparison to 13 microsatellite loci showed that 335 and 359 bp deviate significantly from neutral expectations. Furthermore, a hierarchical gene diversity analysis based on OtsClock1b PolyQ variation revealed that run timing explains 40.9 per cent of the overall genetic variance among populations. By contrast, an analysis based on 13 microsatellite loci showed that run timing explains only 13.2 per cent of the overall genetic variance. Our findings suggest that length polymorphisms in OtsClock1b PolyQ may be maintained by selection and reflect an adaptation to ecological factors correlated with latitude, such as the seasonally changing day length.     

Association between paraoxonase-1 gene Q192R and L55M polymorphisms and risk of gastric cancer: A case-control study from Iran

The aim of the present study was to examine the relation between two paraoxonase1 (PON1) polymorphisms, Q192R and L55M and susceptibility to gastric cancer in an Iranian population. In this case-control study the PON1 polymorphisms were assessed in 90 gastric cancer patients and 90 healthy controls by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. Regarding PON1 Q192R polymorphism, a significant increase in the R allele in the patient group compared with the controls (p value?=?0.0006) While the Q allele was more frequent in the control group. No significant difference was found in the genotype or allele frequency of the L55M polymorphism between healthy individuals and patients with gastric cancer. Our results demonstrated the protective effect of Q allele against gastric cancer.     

Linking intronic polymorphism on the CHD1‐Z gene with fitness correlates in Black‐tailed Godwits Limosa l. limosa

We show that variation in an intronic length polymorphism in the CHD1‐Z gene in Black‐tailed Godwits Limosa l. limosa is associated with fitness correlates. This is the second example of the CHDZ‐1 gene being correlated with fitness, a previous study having established that Moorhens Gallinula chloropus carrying the rare Z* allele have reduced survival. In Godwits, however, carriers of the Z* allele (374 bp) fared better than those with the more frequent Z allele (378 bp) with respect to body mass, plumage ornamentation, reproductive parameters and habitat quality. The Z* allele was found in 14% of 251 adult birds from nature reserves, but was absent from 33 birds breeding in intensively managed agricultural lands. Males and females with the Z* allele had less extensive breeding plumage, and females had a higher body mass, bred earlier and had larger eggs. There were no significant differences in annual survival between birds with and without the Z* allele. DNA isolated from museum skins demonstrated that this polymorphism was present at low frequency in 1929. We speculate that strong asymmetrical overdominance may explain the low frequency of the Z* allele and that genetic linkage to causal genes might be an explanation for the phenotypic correlations. Our findings suggest a degree of cryptic genetic population structuring in the Dutch Godwit population.     

Genetic polymorphism of the kappa-casein gene in Brazilian cattle

Frequencies of kappa-casein gene alleles were determined in 1316 animals from the Brazilian Bos indicus genetic groups (Sindhi cows, Gyr sires, Gyr cows, Guzerat sires, Guzerat cows, Nellore sires, and Gyr x Holstein crossbreds) by means of polymerase chain reaction-restriction fragment length polymorphism analysis using two independent restriction nucleases (Hinf I and HaeIII). The genotyping of kappa-casein alleles (A and B) is of practical importance, since the B allele is found to correlate with commercially valuable parameters of cheese yielding efficiency. The frequencies of the B allele of kappa-casein among breeds ranged from 0.01 to 0.30. The Sindhi breed had the highest frequency for the B allele (0.30), while the frequencies of this allele in other breeds ranged from 0.01 to 0.18. A wide variation in the B allele frequency among B. indicus breeds was found suggesting that molecular selection for animals carrying the B allele could impact breeding programs for dairy production.     

Estimation of allele frequency in pooled DNA by using PCR–RFLP combined with microchip electrophoresis

Biallelic marker, most commonly single nucleotide polymorphism (SNP), is widely utilized in genetic association analysis, which can be speeded up by estimating allele frequency in pooled DNA instead of individual genotyping. Several methods have shown high accuracy and precision for allele frequency estimation in pools. Here, we explored PCR restriction fragment length polymorphism (PCR–RFLP) combined with microchip electrophoresis as a possible strategy for allele frequency estimation in DNA pools. We have used the commercial available Agilent 2100 microchip electrophoresis analysis system for quantifying the enzymatically digested DNA fragments and the fluorescence intensities to estimate the allele frequencies in the DNA pools. In this study, we have estimated the allele frequencies of five SNPs in a DNA pool composed of 141 previously genotyped health controls and a DNA pool composed of 96 previously genotyped gastric cancer patients with a frequency representation of 10–90% for the variant allele. Our studies show that accurate, quantitative data on allele frequencies, suitable for investigating the association of SNPs with complex disorders, can be estimated from pooled DNA samples by using this assay. This approach, being independent of the number of samples, promises to drastically reduce the labor and cost of genotyping in the initial association analysis.     

DNA polymorphism of the RC8 sequence on the short arm of the X chromosome in a French population

Restriction fragment length polymorphism of the RC8 probe, which is loosely linked to the Duchenne muscular dystrophy locus, was studied in a French population. Among 22 females, 18.1% were found to be heterozygous for the two frequent B1 and B2 alleles, and a rare allele was found in 1 woman with a corresponding variant band at 3 kb. Among 18 males, 6 were found to have the B2 allele. The B2 gene frequencies were 0.09 and 0.33 in males and females, respectively. This difference was statistically significant (p less than 0.05), but may nevertheless be fortuitous. There was no significant gene frequency difference between the English and French populations.     

Genetic variations ofCottus nozawae populations from five tributaries of the Shiribetsu River of southern Hokkaido,Japan

To estimate genetic differentiation and heterogeneity in the landlocked river sculpin,Cottus nozawae, between tributary populations in the same river-system, 107 specimens were captured from 5 tributaries of the Shiribetsu river (course length 128 km), Hokkaido Island and surveyed for allozyme variations and restriction fragment length polymorphisms of mitochondrial DNA (mtDNA). Three and two alleles were seen at theIdh-2 andPgm loci, respectively, but only one locus,Idh-2, out of twenty loci examined was regarded as polymorphic, since the frequency of the most common allele did not exceed 0.95. Three different mtDNA haplotypes were detected, there being replacement of them between the tributary populations. Heterogeneities of allele and haplotype frequencies were significant between some tributary populations, suggesting that genetic differentiation has occurred between them.     

Temporal changes in allele frequencies in two European F2 flint maize populations under modified recurrent full-sib selection

Selection and random genetic drift are the two main forces affecting the selection response of recurrent selection (RS) programs by changes in allele frequencies. Therefore, detailed knowledge on allele frequency changes attributable to these forces is of fundamental importance for assessing RS programs. The objectives of our study were to (1) estimate the number, position, and genetic effect of quantitative trait loci (QTL) for selection index and its components in the base populations, (2) determine changes in allele frequencies of QTL regions due to the effects of random genetic drift and selection, and (3) predict allele frequency changes by using QTL results and compare these predictions with observed values. We performed QTL analyses, based on restriction fragment length polymorphisms (RFLPs) and simple sequence repeats (SSRs), in 274 F_2:3 lines of cross KW1265 × D146 (A × B) and 133 F_3:4 lines of cross D145 × KW1292 (C × D) originating from two European flint maize populations. Four (A × B) and seven (C × D) cycles of RS were analyzed with SSRs for significant allele frequency changes due to selection. Several QTL regions for selection index were detected with simple and composite interval mapping. In some of them, flanking markers showed a significant allele frequency change after the first and the final selection cycles. The correlation between observed and predicted allele frequencies was significant only in A × B. We attribute these observations mainly to (1) the high dependence of the power of QTL detection on the population size and (2) the occurrence of undetectable QTL in repulsion phase. Assessment of allele frequency changes in RS programs can be used to detect marker alleles linked to QTL regions under selection pressure. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

C9ORF72 Repeat Expansion in Australian and Spanish Frontotemporal Dementia Patients

A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in ‘non-expansion’ patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5–17% of patients (21–41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine ‘expansion-positive’ patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an ‘intermediate’ allele with a mean size of only ∼65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of ‘non-expansion’ FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ∼65 repeats may be sufficient to cause disease.     

Frequency and rearrangements of alleles of proto-oncogene c-Ha-ras-1 and their association with development of various malignant tumors in man

The c-Ha-ras-1 locus in 84 cancer patients was examined for allelic restriction fragment length's polymorphism, as well as for distribution of four common c-Ha-ras-1 alleles (a1, a2, a3 and a4) in lung, ovarian and thyroid cancer patients. In approximately half (8 out of 15) lung and ovarian carcinomas possessing a4 allele, alterations in the Ha-ras locus (deletion, amplification and change in allele length) were detected, as compared to 2 cases of rearrangements out of 40 tumors lacking the a4 allele. An increased a4 allele frequency was found in individuals with lung and ovarian carcinomas, as compared to both controls--summarized literature data, and thyroid cancer patients. On the other hand, homozygosity for the a2 locus, resulting from deletion in another allele, and increased a2 allele frequency in thyroid cancer patients were observed. Thus, a4 and a2 alleles of the c-Ha-ras-1 may perhaps be viewed as genetic markers of predisposition to lung, ovarian and thyroid cancer, respectively, in combination with other clinical parameters.