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.     

X chromosome restriction fragment length polymorphisms in five racial groups: rare variant detected with the RC8 (DXS9) probe in the Marathi population, India

Restriction fragment length polymorphisms were investigated in five racial groups using the X chromosome probes DXS9 and DXS7. The allele frequencies of these polymorphisms showed significant differences and both DNA fragments were found to be highly polymorphic in the populations of south and southeast Asia. In the Marathi population of India, a rare allele B*3 (3 kilobases; kb) and an altered 7-kb fragment instead of the 6.6-kb constant band were found with DXS9. This is the first time that the rare B*3 allele is found in a non-European population.     

Polymorphisms of apolipoproteins A-IV and E in a Turkish population living in Germany

Human apolipoproteins (apo) E and apo A-IV are polymorphic with significantly different allele frequencies among different ethnic groups. Whereas the variation at the apo E gene locus affects plasma cholesterol levels in all populations studied so far and is associated with longevity in Caucasians, the influence of the common apo A-IV polymorphism on plasma lipoproteins has not been unanimously accepted. We have therefore determined the common apo E and apo A-IV polymorphisms by isoelectric focusing, calculated the respective allele frequencies and studied their effects on plasma lipoproteins in a random sample of 240 nonrelated Turkish subjects (141 males, 99 females) living in Germany and originating from central and eastern Anatolia. When compared with the German population and other Caucasians in Europe a prominence of the apo ɛ3 allele frequency (0.885) was accompanied by a decrease in the frequencies of both the apo ɛ2 allele (0.048) and the apo ɛ4 allele (0.067). Thus, the Turkish population studied here clustered with populations mainly from southern Europe and Japan, which have low ɛ2 and ɛ4 allele frequencies. Also, the frequency of the A-IV-1 allele was higher (0.967) and that of the A-IV-2 allele lower (0.033) in the Turkish subjects studied than in other populations. At an average level of total cholesterol of 194.5 ± 45 mg/dl, no significant influence of the A-IV alleles on plasma lipoproteins was seen. However, apo E and apo B differed significantly between apo E phenotypes, with high levels of apo E and low levels of cholesterol and apo B in carriers of the ɛ2 allele, and vice versa for the ɛ4 allele. The average cholesterol excess for the ɛ2 allele was –7.95 mg/dl, for the ɛ3 allele, –1.34, and for the ɛ4 allele, +14.15 mg/dl. Thus, despite the unusual frequency distribution of the apo E alleles, their effects on plasma lipoproteins are within the range reported for other populations in Europe. Received: 10 April 1995 / Revised: 25 March 1996     

The ''cation-dependent'' mannose 6-phosphate receptor binds ligands in the absence of divalent cations

EcoRI restriction fragment length polymorphisms (RFLP) at the human c-mos locus were analysed in DNAs of normal individuals and tumour patients. Two alleles with fragment lengths of 2.6 kb (A1) and 5.6 kb (A2) respectively were detected. The allele distribution among the tumour group was similar to that of the control group. No difference was found between the allele frequencies in leucocytes and tumour tissue DNA of the same patients.     

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).     

Human histone gene organization : Identification of a histone gene polymorphism prevalent in a black population

Analysis of the restriction enzyme digests of total genomic DNAs from a broad spectrum of human cell lines and from individuals with different genetic backgrounds, by hybridization with a series of cloned human histone sequences, indicated restriction site polymorphisms (RSPs) for two adjacent human histone genes which reside on chromosome 1. In most cell lines and individuals examined we observed a single 2.05 kb H4 histone HindIII fragment and a 7.0 kb H3 histone HindIII fragment. In contrast, the polymorphisms were manifested as a 2.15 kb H4 HindIII fragment and a 9.1 kb H3 HindIII fragment. From population studies, we were able to show that there is no linkage disequilibrium between these two polymorphic restriction sites. Nor was there any apparent correlation between the presence of the H3/H4 histone polymorphisms and maintenance of the transformed karyotype, passage in culture, transformation or tumor progression. These chromosome 1 H3 and H4 histone gene polymorphisms are common in the American Black population and, in our survey of individuals, were not found in the American Caucasian population. Among the American Blacks studied, the frequency of the H3 HindIII(-) allele is 43% and of the H4 HindIII(-) allele 30%. In limited family studies, we were unable to detect recombination between these two physically linked alleles.     

Molecular basis of five apolipoprotein B gene polymorphisms in noncoding regions

Restriction fragment length polymorphisms (RFLPs) are useful in linkage and clinical association studies of human diseases. In this report, we characterize the molecular basis and frequencies of two new RFLPs, AvaII and BalI, two previously reported RFLPs, HincII and PvuII, and one new sequence polymorphism in the human apolipoprotein B gene. For the AvaII RFLP, the two alleles yield either a 1 kb fragment or 0.7 and 0.3 kb fragments, and have frequencies of 20% and 80%, respectively. The polymorphic site is about 4 kb upstream of exon 1. For the BalI RFLP, the two alleles yield either a 4.9 or 6.2 kb fragment, and have about equal frequencies. The polymorphic site is within an Alu sequence in intron 20, 146 bp 5' to exon 21. The BalI recognition sequence TGGCCA is replaced by TAGCCA. For the HincII RFLP, the two alleles yield either a 1.7 or 1.3 kb fragment and have frequencies of 80% and 20%, respectively. The polymorphic site is in intron 4, 171 bp 3' to exon 4. The HincII recognition sequence GTTAAC, present in the minor allele, is replaced by GTTACC. HincII fragments of 7.4 and 7.0 kb, previously reported for this polymorphism, are the result of partial digestion at the invariant HincII site in intron 3, 334 bp 3' to exon 3. For the PvuII RFLP, the two alleles yield either a 7.5 or 5.5 kb fragment and have frequencies of 96% and 4%, respectively. The polymorphic site is within an Alu sequence in intron 4, 523 bp 5' to exon 5.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Turkish population data on the factor XIII Val34Leu,glycoprotein (GP)Ibalpha Kozak and P-selectin glycoprotein ligand 1 (PSGL-1) loci

We determined the allele and genotype frequencies of three PCR-based gene polymorphisms factor XIII (FXIII) Val34Leu, glycoprotein (GP) Ibalpha Kozak and P-selectin glycoprotein ligand 1 (PSGL-1) in the Turkish population (n = 126 for FXIII Val34Leu, n = 110 for GPIbalpha Kozak and n = 203 for PSGL-1). To detect these polymorphisms, DNA was extracted from venous blood. Genomic DNA samples were replicated and analysed by a polymerase chain reaction (PCR) method. PCR products were digested by restriction endonuclease enzymes for FXIII Val34Leu and GPIbalpha Kozak. PSGL-1 was analysed by variable number of tandem repeats (VNTR). Allele frequencies of V (Val) and L (Leu) were found to be 0.805 and 0.195 respectively for the FXIII Val34Leu polymorphism. No significant difference was observed between French and Turkish populations for FXIII Val34Leu. Allele frequencies of T and C were calculated to be 0.873 and 0.127 for the GPIbalpha Kozak polymorphism and no significant difference was found between Turkish and French populations. In contrast, the difference between Turkish and Japanese populations was statistically significant (p<0.0001). In the PSGL-1 group, allele frequencies of A, B and C were calculated as 0.818, 0.160, 0.022 respectively. For the PSGL-1, although the difference between Turkish and French populations was not significant, the difference between the Turkish and Japanese was extremely significant (p<0.0001). In conclusion, a Turkish population database has been established for three gene polymorphisms.     

Allele frequencies of single nucleotide polymorphisms in the second exon of the myoglobin gene among the Japanese

The difference in the allele frequencies of two single nucleotide polymorphisms (SNPs) in the second exon of the myoglobin gene between Japanese and other populations is reported. These SNPs are the substitutions of (A79G) and (T109C), and they were investigated by a single polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing. The substitutions were always linked and two alleles were found in the samples used: the A-T allele with no substitution at positions (79A) and (109T) and the G-C allele with substitutions of (79G) and (109C). The frequencies of these alleles were 0.755 and 0.245, respectively, and they were found to be in Hardy-Weinberg equilibrium. The distribution of alleles in the Japanese population was significantly different from that reported among whites, blacks, and Hispanics (p < 0.0001).     

Restriction fragment length polymorphisms at the human parathyroid hormone gene locus

Summary Two common Pst I and Taq I restriction enzyme fragment length polymorphisms (RFLPs) were detected at the human parathyroid hormone (PTH) gene locus. The allele frequencies in a Northern German population were 0.578/0.422 (Pst I) and 0.628/0.372 (Taq I). The allele distributions follow Hardy-Weinberg expectations of equilibrium in the population. The Mendelian nature of the polymorphisms were confirmed in family studies.     

Allele frequencies and linkage disequilibrium of polymorphic DNA markers of the Huntington disease region in the German population

Allele frequencies of 14 different restriction fragment length polymorphisms from 12 DNA markers within the Huntington disease (HD) region were evaluated in the German population. No significant differences from published data of allele frequencies from chromosomes of Caucasian ancestry were found. The analysis of eight DNA polymorphisms in 87 HD families of German origin revealed significant non-random association with the HD locus and the D4S95 locus (p674/AccI/MboI), a result that is consistent with all other published studies. These results are confirmed by the fact that the HD gene maps to this region.     

Arylamine N-acetyltransferase 2 genotypes in a Mexican population

The acetylating activity of N-acetyltransferase 2 (NAT2) has critical implications for therapeutics and disease susceptibility. To date, several polymorphisms that alter the enzymatic activity and/or protein stability of NAT2 have been identified. We examined the distribution and frequency of NAT2 genotypes in the Mexican population. Among 250 samples amplified and sequenced for the NAT2 gene, we found seven different SNPs; the most frequent allele was 803 A>G (35.8%), followed by 282 C>T, 341 T>C, and 481 C>T. There were no differences in the distribution of SNPs between healthy subjects and cancer patients. These eight polymorphisms defined 26 diplotypes; 11.6% were wild type (NAT2*4/NAT2*4), while the most common diplotype was NAT2*4/NAT2*5B, present in 17.2%. We did not identify other common polymorphisms. The results were compared with the NAT2 SNPs reported from other populations. All but the Turkish population was significantly different from ours. We conclude that the mixed-race Mexican population requires special attention because NAT2 genotype frequencies differ from those in other regions of the world.     

Investigation of factor VIII:C gene restriction fragment length polymorphisms and search for deletions in hemophiliac subjects in Algeria

Summary The frequency of alleles for intragenic (intron 17 and intron 25) and extragenic (DXS15 and DXS52) F8C RFLPs was investigated in the Algerian population. Altogether 287 X chromosomes (97 males and 95 females) were studied. The allele frequencies found with the two intragenic F8C RFLPs were not substantially different from those reported in a Mediterranean population. At the highly polymorphic extragenic DXS52 locus the distribution in Algeria differed from that found in France. A new allele (14kb), called 1 DZ, was found in 3.1% of the chromosomes. Fifty-one families with hemophilia A were studied with the same probes (374 subjects). Of the females, 94% were informative for at least one intra- or extragenic RFLP. Two recombinations were found between DXS52 and F8C, of which one occurred between the DXS15, DXS52 block and F8C, indicating that the two anonymous loci are on the same side of the F8C gene. Only two obvious gene deletions were observed in 73 unrelated hemophiliacs: one encompassed exons 14–22 (about 4.3 kb of cDNA and 36kb of genomic DNA); the other removed the last exon (exon 26, representing 2 kb of cDNA).     

Phenylketonuria mutations in Germany

We report the spectrum of mutations and associated modified haplotypes in patients with phenylketonuria living in Germany. A total of 546 independent alleles was investigated, including 411 of German and 65 of Turkish descent. Mutations were identified for 535 PKU alleles (98%) and there were 91 different mutations. The most common mutation was R408W on 22% of alleles. Two mutations, IVS12+1G→A and IVS10–11G→A accounted for just under 10% of alleles, whereas the remaining mutations were found at relative frequencies of 6% or less; 43 mutations were observed once only. IVS10–11G→A was the most common mutation (38% of alleles) in the subgroup of patients of Turkish descent. Modified haplotypes were determined from the analysis of four silent mutations, three diallelic restriction fragment length polymorphisms, a variable number of tandem repeats minisatellite and a short tandem repeat microsatellite in the phenylalanine hydroxylase gene, showing that a considerable proportion of mutations must have recurred in independent founders; other mutations may have changed chromosomal haplotype backgrounds by gene conversion. The spectrum of PKU mutations in Germany reflects the history of a heterogenous Central European population living at the crossroads of migration throughout the centuries. Received: 11 January 1999 / Accepted: 11 March 1999     

Apolipoprotein B signal peptide polymorphism: distribution and influence on lipid parameters in Tunisian population

Apolipoprotein B (apo B) is the major protein component of LDL, VLDL and chylomicrons. Numerous polymorphisms of the apolipoprotein B gene have been described. Particularly, the insertion/deletion polymorphism located in the coding part of the signal peptide of apo B, associated with modification of lipid concentrations and the risk of cardiovascular disease, has been reported in the general population. No such study in the Tunisian population has been performed. The aim of our study was to assess the effect of insertion/deletion polymorphism of the apolipoprotein B gene on lipid levels in a sample of the Tunisian population. A total of 458 unrelated subjects (321 men and 137 women) were included. The insertion/deletion polymorphism was determined by electrophoresis on polyacrylamide gels after PCR amplification. The relative frequencies of the Ins and Del alleles were 0.74 and 0.26, respectively. These frequencies were similar to those found in other Caucasian populations. There was no significant difference in serum TC, TG, and HDL-C levels due to the influence of the genotypes. However, significant variation among the three genotypes was seen for LDL-cholesterol (p<0.001) and apo B (p<0.001) levels. Individuals homozygous for the Del allele had higher levels than individuals homozygous for the Ins allele, while individuals heterozygous for both alleles exhibited intermediate levels. When the data were analyzed in men and women separately, a similar effect was seen in both groups. Our results show that distribution of apo B insertion/deletion polymorphism in Tunisians is similar to other Caucasian population and confirm the reported association with serum LDL-cholesterol and apo B concentrations.     

TNF promoter ?308 A/G and ?238 A/G polymorphisms and juvenile idiopathic arthritis: a meta-analysis

The aim of this study was to determine whether the tumor necrosis factor (TNF) promoter polymorphisms confer susceptibility to juvenile idiopathic arthritis (JIA). A meta-analysis was conducted on the A allele of the TNF -308 A/G and -238 A/G polymorphisms. The nine comparison studies including 1,132 JIA patients and 1,663 controls were included in the meta-analysis and consisted of 7 European, 1 Mexican, and 1 Turkish population. No association was found between JIA and the TNF -308 A allele and the TNF -238 A allele (odds ratio [OR] = 1.211, 95 % confidence interval [CI] = 0.917-1.598, P = 0.177; OR = 1.135, 95 % CI = 0.603-1.861, P = 0.615, respectively). Stratification by ethnicity did not show the association of the TNF -308 and -238 polymorphisms with JIA in Europeans. Mexicans were found to have lower prevalences of A alleles (2.9, 4.1 %) of the TNF -308 A/G and -238 A/G polymorphisms than any other population studied, and the Turkish population the highest (31.2, 26.9 %). This meta-analysis shows no association between the A alleles of the TNF -308 A/G or -238 A/G polymorphisms and JIA in Europeans, but that the prevalences of these alleles are ethnicity dependent.     

Comparing the frequencies of restriction fragment length polymorphisms for dystrophin gene in Chinese with those from Japanese and Caucasian populations

The restriction fragment length polymorphisms distribution and frequency of dystrophin gene in Chinese were studied by using 14 subclones of the entire 14kb cDNA for the dystrophin as hybridization probes. Allelic fragments were detected in hybridization patterns of PvuⅡ/la, Taq Ⅰ/2b-3, Taq Ⅰ/5b-7, and Xba Ⅰ/10. Among them, the allelic fragments (26kb and 3.8kb) in PvuⅡ/2b-3 pattern and the allelic fragments (10.0kb and 8.4kb) in Taq Ⅰ/5b-7 patterns had never been reported previously. Compared with the data from Caucasians and Japanese, it indicated that there was a significant difference (P<0.01) of the allelic fragment frequency in Taq Ⅰ/2b-3 and Xba Ⅰ/10 patterns between Chinese and Caucasians. The frequencies of allelic fragments A2 (5.6kb) in Taq Ⅰ/8 and A2 (10.Tkb) in EcoR Ⅴ/9 were high in Caucasians, yet had not been detected in Chinese, the differences were also highly significant. But in Chinese and Caucasians, the B1B2 allelic frequencies in Taq Ⅰ/5b-7 are the same. As to the frequency of the allelic fragments A1A2 and B1B2 in Pvu Ⅱ/la, there was no significant difference between Chinese and Japanese.     

CYP2A6 polymorphism reveals differences in Japan and the existence of a specific variant in Ovambo and Turk populations

CYP2A6 is a polymorphic enzyme, and CYP2A6 genotype has been shown to be associated with smoking habits and lung cancer. We investigated CYP2A6 polymorphism in Japanese from four different geographic areas of Japan and in the Ovambo and Turk populations. Using two polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLPs), we identified the functionally important variants of CYP2A6: *1A, *1B, *1F, *1G, *4A, and *4D. In the Japanese population the highest frequencies of the CYP2A6*1A allele were observed in subjects from the Fukuoka (Kyushu Island) and Ehime (Shikoku Island) prefectures, whereas subjects in Shimane and Tottori (both located on the Japan Sea side of Honshu Island) showed the highest frequencies of the CYP2A6*1B allele. In the Tottori and Shimane groups no subject was homozygous for the CYP2A6*4A allele, a whole gene deletion type that is prevalent among Asians. In the Ovambo and Turk populations the CYP2A6*1A allele was predominant. Furthermore, two alleles undetected in the Japanese were observed in these latter two ethnic groups: CYP2A6*1G was found solely in the Ovambos, and CYP2A6*1F was found solely in the Turks. The present study is the first to show interprefecture differences in CYP2A6 polymorphism in Japanese who live in relatively close but distinct geographic areas; this is also the first study to evaluate CYP2A6 variations among these Japanese and the Ovambo and Turk populations. The distribution results of these alleles could help to define the true significance of CYP2A6 polymorphism as a genetic susceptibility marker in worldwide populations.     

Effects of intragenic variability at 3 polymorphic sites of the apolipoprotein B gene on serum lipids and lipoproteins in a multiethnic Asian population.

We determined the allelic (X+/X-, M+/M-, and E+/E-) distribution frequencies of the XbaI, MspI, and EcoRI restriction fragment length polymorphisms (RFLPs) in the apolipoprotein B gene in a control group of 374 healthy Chinese, Malays, and Indians and in a hyperlipidemic cohort of 131 Chinese patients. Covariability between the RFLPs and serum lipid, lipoprotein, and apolipoprotein concentrations was also studied. We found a lower frequency (average 0.0829) of the X+ allele and higher frequencies of the E+ (average 0.9452) and M+ (average 0.9772) alleles in our study population compared with frequencies reported in other populations. The 3 polymorphic sites did not contribute to significant variations in lipid levels (p > 0.1 in all cases). Also, there was no significant variation in genotype frequencies between the control subjects and the hyperlipidemic subjects. Despite their relative close proximity within the APOB gene sequence, the 3 polymorphic sites did not show any significant linkage disequilibrium. However, the presence of the X+ cutting site was in linkage disequilibrium with the Del allele of the 5' insertion-deletion polymorphism and the E-allele was in linkage disequilibrium with the 3' VNTR located near the 3' end of the coding region of the APOB gene.