Population genetics of alpha-1-antitrypsin polymorphism in US whites, US blacks and African blacks.

An isoelectric focusing (IEF) procedure in an ultra-narrow pH range, 4.2-4.9, has been utilized to detect alpha 1-antitrypsin or alpha 1-protease inhibitor (PI) allele products in 2 US white and 3 US black populations as well as 1 native African black population. In addition to the 3 common alleles PI*M1, PI*M2 and PI*M3, products of the 4th allele PI*M4 have been identified in US whites at low-level frequency. The presence of the PI*S, PI*Z and PI*I alleles has also been verified in our population samples. While the PI*S allele is present at a polymorphic level in US whites, it is only present sporadically in US blacks and is completely absent in African blacks. The PI*Z allele was not detected in the black populations tested. The PI allele frequency data have been used to calculate white admixture in US blacks.     

Study of five haemogenetic markers (Gc, C3, Bf, Ag, and GALT) in six Indonesian populations and in 12 subgroups of Balinese

In various ethnic groups of the Indonesian archipelago and of Bali, the polymorphisms of the serum proteins Gc globulin (vitamin D-binding protein), C3 (complement component 3), Bf (complement factor B), Ag x,y (lipoprotein allotypes), and of the red cell enzyme system GALT (galactose-1P-uridyltransferase) were analysed. Among the studied proteins, the Gc system was the most informative one for the anthropologist. Besides considerable differences of frequencies of the common alleles Gc*1F, Gc*1S and Gc*2, a number of rare alleles (1A1, 1A3, 1A8, 1A9, 1A12, 1C2, 1C21, 1C24, and 2C8) and some new ones (1C28, 1C29, 1C30, 2C9) were observed. The presence of Gc*1A1 demonstrates the relationship to the Australo-Melanesian populations, but Mongolian variants (1A3, 1A8, 1A9, 1C2) were also encountered. Within the C3 system a very high frequency of the C3*S allele was observed in all populations. The rare alleles C3*F0.55, C3S1, and C3*S0.5 were observed in some groups. A new allele (C3*F0.35) was detected in a Chinese individual and in a nobleman from Bali. The frequency of the Bf*F allele was rather low in general, and the Bf*S0.7 allele was found in three Indonesian individuals only. The Ag*(x) frequencies were rather high, as it is known for Asiatic populations. Variability among subgroups was not very pronounced. The GALT*2 allele (Duarte variant of the enzyme) was observed very rarely; however, it was present in several populations. Enzyme activities could not be determined, and therefore we cannot tell whether the galactosaemia gene (GALT*0) was present or not.     

Protein polymorphism in quail populations selected for large body size

The polymorphism of five enzyme loci (amylase, alkaline phosphatase, albumin, for 4-week body weight was compared to that of the unselected control line (C). Three loci in the C line and two in the P line demonstrated polymorphism. Plasma amylase was separated into six bands and zymograms were classified on the basis of these bands into nine phenotypes. Three of the nine types were of relatively high activity and six were of relatively low activity. All nine types were found in the C line, whereas, all birds of the P line had only the most active type. Two alkaline phosphatase alleles (Akp-2B and Akp-2C) were segregating in the C line. Gene frequencies of alkaline phosphatase for the Akp-2B allele were 0.92 in the C line and 1.00 in the P line. Two albumin alleles (AlbQ1 and AlbQ2) were segregating in both populations. Gene frequencies for the AlbQ1 allele were 0.74 in the C line and 0.81 in the P line. Two red cell esterase-D alleles (Es-DF and Es-DS) were segregating in both populations. The gene frequency for the Es-DS allele (0.61) was higher than that of the Es-DF allele in the C line. In the P line the frequency of the Es-DF allele was higher than that of the Es-DS allele. Heterozygosities of the C and P lines were estimated as 0.2258 and 0.1560 respectively. The relative inbreeding coefficient of the P line, calculated from heterozygosities was 0.31.     

Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations.

CYP2C9 is the major P450 2C enzyme in human liver and contributes to the metabolism of a number of clinically important substrate drugs. This polymorphically expressed enzyme has been studied in Caucasian, Asian, and to some extent in African American populations, but little is known about the genetic variation in Native American populations. We therefore determined the 2C9*2 (Arg144Cys) and 2C9*3 (Ile359Leu) allele frequencies in 153 Native Canadian Indian (CNI) and 151 Inuit subjects by PCR-RFLP techniques. We also present genotyping data for two reference populations, 325 Caucasian (white North American) and 102 Chinese subjects. Genotyping analysis did not reveal any 2C9*4 alleles in the CNI, Inuit, Caucasian, or Chinese individuals. The 2C9*2 allele appears to be absent in Chinese and Inuit populations, but was present in CNI and Caucasian subjects at frequencies of 0.03 and 0.08-0.15, respectively. The 2C9*3 allele was not detected in the Inuit group, but occured in the CNI group (f = 0.06) at a frequency comparable to that of other ethnic groups. This group of Inuit individuals are the first population in which no 2C9*2 or *3 alleles have been detected so far. Therefore, these alleles may be extremely rare or absent, and unless other novel polymorphisms exist in this Inuit group one would not anticipate any CYP2C9 poor metabolizer subjects among this population.     

CCR2-64Ⅰ在中国南方14个少数民族群体中的分布

为调查HIV-1感染相关等位基因CCR2-64Ⅰ在我国南方14个少数民族群体的频率和多态性分布, 从上述人群外周血中抽提基因组DNA, 采用PCR和PCR-RFLP等方法进行基因分型。在791例调查对象中, 636例是野生纯合子基因型, 104例为杂合子基因型, 51例为突变纯合子基因型。上述各群体等位基因型的分布符合Hardy-Weinberg平衡。14个民族群体的平均突变基因频率为13.6％, 等位基因频率范围分布在1.6％~30.3％之间, 14个民族群体之间突变基因频率具有显著差异(P<0.05)。广西壮族群体CCR2-64Ⅰ突变基因频率最低, 为1.6％, 云南的六库傈僳族频率最高, 为30.3％。12个群体的突变基因频率均低于中国汉族健康群体, 南方3个少数民族群体基因突变频率显著低于西南11个少数民族群体, 该突变基因在艾滋病发病过程中的影响值得进一步深入研究。     

Frequency and fitness cost of resistance to Bacillus thuringiensis in Chrysomela tremulae (Coleoptera: Chrysomelidae)

The "high dose-refuge" (HDR) strategy is commonly recommended and currently used for delaying or preventing pest adaptation to transgenic plants producing Bacillus thuringiensis (Bt) toxins. The efficiency of this strategy depends, among other factors, on the initial frequency of Bt resistance alleles and on the fitness costs associated with these alleles. Two years ago, an allele conferring resistance to Bt poplar was detected in a French population of the poplar pest Chrysomela tremulae F. Although this pest had never been subjected to Bt selection pressure due to human activities, the frequency of this allele was estimated at 0.0037, with a 95% credible (CI) interval of 0.00045-0.0080. We investigated the frequency of this allele in a second sample of C. tremulae collected more than 500 km from the site of the initial population. The estimated frequency in this sample was 0.0113 (95% CI 0.0031-0.0247), reinforcing the conclusion that resistance to Bt plants may be present at detectable frequencies in pest populations before selection resulting from pest management by humans. The frequency of the Bt resistance allele over the two samples was 0.0049 (95% CI 0.0020-0.0091). We also followed five laboratory lines in which the frequency of this allele was initially fixed at 0.500. After five generations maintained on non-Bt poplar leaves, the frequency of this allele decreased in all lines, whereas allelic frequencies at a neutral locus were unaffected. Thus, the Bt resistance allele detected in French populations of C. tremulae is probably associated with a fitness cost.     

中华稻蝗四个种群的遗传分化

采用水平淀粉凝胶电泳技术研究中华稻蝗(Oxya chinensis)四个种群的12个基因座位,探讨其遗传分化.这四个种群分别采自内蒙古呼和浩特、山西代县、山西太原和陕西西安.Ck和Mdh-2在四个种群中均为单态,其余的基因座位至少在一个种群内有两个以上的等位基因;在Ldh和Mdh-1的等位基因频率呈现梯度分布趋势.多态基因座位百分率(P)和平均每个基因座位的等位基因数目(A)分别为58.3%-66.7%和2.2-2.8,平均杂合度为Ho=0.173-0.240.除Gpi,Hk-2,Idh,Ldh和Mdh-1在部分蝗虫种群符合Hardy-Weinberg平衡外,其余绝大多数基因座位的基因型频率显著偏离Hardy-Weinberg平衡.四个种群间FST平均值不存在显著差异(FST=0.0510,P＞0.05),结合高的Nei's遗传一致度(I＞0.97)可知,种群之间遗传分化不明显.我们认为人类的农业活动可能促进了种群间的基因交流,从而降低了分化程度[动物学报50(2)187-192,2004].     

Analysis of the DRD4 gene polymorphism in populations of Russia and neighboring countries

Allele and genotype frequencies of the VNTR polymorphism in the third exon of human DRD4 gene were determined in 544 individuals living in Russia (Russians, Bashkirs, Tatars, and Mordovians) and in the neighboring countries (Kazakhs and Ukrainians). The data obtained were compared with the allele frequency distribution patterns reported for the populations of Eurasia. Similarly to other Eurasian populations, in our population samples R4 allele was prevalent (64 to 87%). The frequency of this allele in the populations of Western Europe constitute 61 to 71%, while in the populations of Asia it varies from 74 to 96%. In this respect, the populations studied occupied the intermediate position. In the samples examined the R7 allele frequency decreased from 7% in Ukrainians to 1% in Bashkirs, while in Kazakhs and Mordovians the allele was absent. This finding was consistent with the R7 allele distribution pattern in the populations of Eurasia, characterized by higher frequency in the West and lower frequency or absence of the allele in the East. In the group of 22 Eurasian populations, the R7 allele frequency negatively correlated with the frequency of the R4 allele (r = -0.86 at P < 0.001). Unlike the R4 and R7 alleles, the frequency of which changed in the eastward direction, the R2 allele frequency distribution displayed slightly expressed latitudinal increase southwards. The DRD4 genotype distribution deviated from the equilibrium in most of the samples examined. In some samples, statistically significant increase of the R2/R2 homozygotes frequency was demonstrated. One of the possible explanations of this phenomenon is assortative mating with respect to phenotypic (behavioral) allele manifestation. The data obtained can serve as the basis for the investigation of the possible role of the DRD4 alleles as the risk factors for the development of alcoholism and other types of addictions.     

Protein polymorphism in quail populations selected for large body size

The polymorphism of five enzyme loci (amylase, alkaline phosphatase, albumin, for 4-week body weight was compared to that of the unselected control line (C). for 4 week body weight was compared to that of the unselected control line (C). Three loci in the C line and two in the P line demonstrated polymorphism. Plasma amylase was separated into six bands and zymograms were classified on the basis of these bands into nine phenotypes. Three of the nine types were of relatively high activity and six were of relatively low activity. All nine types were found in the C line, whereas, all birds of the P line had only the most active type. Two alkaline phosphatase alleles (Akp-2^B and Akp-2^C) were segregating in the C line. Gene frequencies of alkaline phosphatase for the Akp-2^B allele were 0.92 in the C line and 1.00 in the P line. Two albumin alleles (Alb^Q1 and Alb^Q2) were segregating in both populations. Gene frequencies for the Alb^Q1 allele were 0.74 in the C line and 0.81 in the P line. Two red cell esterase-D alleles (Es-D^F and Es-D^s) were segregating in both populations. The gene frequency for the Es-D^s allele (0.61) was higher than that of the Es-D^F allele in the C line. In the P line the frequency of the Es-D^F allele was higher than that of the Es-D^s allele. Heterozygosities of the C and P lines were estimated as 0.2258 and 0.1560 respectively. The relative inbreeding coefficient of the P line, calculated from heterozygosities was 0.31.     

Effects of temperature on physiology and reproductive success of a montane leaf beetle: implications for persistence of native populations enduring climate change

Understanding how climate change impacts natural systems requires investigations of the effects of environmental variation on vulnerable species and documentation of how populations respond to change. The willow beetle Chrysomela aeneicollis is ideal for such studies. It lives in California's Sierra Nevada on the southern edge of its worldwide range. Beetles experience elevated air temperatures during summertime egg laying and larval development. Exposure to these temperatures causes physiological stress, which may reduce reproductive success and endanger populations. The glycolytic enzyme phosphoglucose isomerase (PGI) is a marker of temperature adaptation in C. aeneicollis. PGI allele frequency varies across a latitudinal gradient: allele 1 is common in Rock Creek (RC), which is cooler and to the north, and allele 4 is common in Big Pine Creek (BPC), which is warmer and to the south. In populations that are intermediate in geography and climate (e.g., Bishop Creek [BC]), PGI-4 frequency increases from north to south such that alleles 1 and 4 are in relatively equal frequency in southern BC. Over the past decade, Sierra Nevada beetle populations have colonized high elevations and have become extinct at lower elevations where they were once common. In BC, the magnitude of PGI allele frequency fluctuations among life-history stages is related to maximal air temperature, with the frequency of PGI-4 increasing after the hottest part of summer. To identify mechanisms that may cause shifts in PGI allele frequency, we measured metabolic rate and fecundity for beetles collected at BC. Metabolic rate of males and females was measured at 20 degrees and 36 degrees C using flow-through respirometry. To measure laboratory fecundity, mating pairs were acclimated for 4 h each afternoon at a control temperature (20 degrees C) or at mildly elevated temperatures (26 degrees or 32 degrees C) and number of eggs laid was counted daily for 24 d, after which tissue levels of 70-kD heat shock proteins (Hsp70) were determined. Previous studies had demonstrated differences in Hsp70 expression among PGI genotypes at these temperatures. To measure field fecundity, mating pairs from BC were transplanted to similar elevations in BPC, BC, and RC and were monitored in situ for 24 d. Metabolic rate was higher for PGI 4-4 genotypes than for PGI 1-4 or PGI 1-1 individuals at 36 degrees C but not at 20 degrees C. In contrast, laboratory fecundity was greatest for females possessing PGI-1, independent of acclimation temperature. At the end of the laboratory fecundity experiment, Hsp70 expression was positively related to fecundity, suggesting minimal reproductive cost of upregulation of heat shock proteins in response to mild heat stress. In the field, fecundity was highest for PGI 1-1 and PGI 1-4 individuals in RC and PGI 4-4 individuals in BPC and was similar for all genotypes in BC. Thus, fecundity in nature was greatest for the genotypes that were most common in each area. Taken together, data reported here suggest that hot, dry summers in the Sierra Nevada may result in an increase in frequency of the PGI-4 allele and shifts to higher elevations for C. aeneicollis populations.     

Genetic diversity of six populations of Atractomorpha sinensis and Atractomorpha peregrina in Shanxi Province, China

Ten enzymes (AAT,CK,G3PDH,HEX,IDH,LDH,MDH,ME,PGI,PGM)were examined using horizontal starch gel electrophoresis to estimate the levels of genetic variation within and among six natural populations of two grasshopper species Atractomorpha sinensis and A.peregrina from Shanxi,China.The collecting sites were geographically distant from each other from south to north:Quwo district,Linfen city;Xiangyuan county,Changzhi;Jinyuan district,Taiyuan city;Yuanping county,Xinzhou city and Fanshi county of Xinzhou.A.sinensis showed 43 alleles at 16 loci but A.peregrine showed 39 alleles at 15 loci (ldh-1 was deficient).The zymograms showed that some common alleles were shared at several loci in these two species (Aat-1-b,Aat-2-b,G3pdh-a,Ck-1-b and Ldh-b).However,Hex-1-a,Hex-2-a,Hex-3-a,Idh-2-b,Mdh-2-b,Mdh-1-f Pgi-b,Pgm-b had common alleles in A.sinensis and Hex-1-b,Hex-2-b,Hex-3-b,Idh-2-a,Mdh-2-a,Mdh-1-d,Pgi-a,Pgm-c were of high frequency in A.peregrine instead.Most of the observed genotype frequencies were found to significantly deviate from the Hardy-Weinberg expectations in both species.A tendency of clinal distribution of allele frequency was observed at three loci.The frequency of the moderately migrating allele Me-c (0.318-0.740)in A.peregrina,Hex-1-a (0.800-1.000)and Ldh-b (0.487-0.750)in A.sinensis demonstrated increased frequency from north to south.Such tendency suggests that the allele frequency in these three loci may be correlated with the species'geographic distributions.A.sinensis showed higher genetic diversity than A.peregrina as indicated by higher mean number of alleles per locus (A=1.9-2.3 in A.sinensis and 1.7-2.2 in A.peregrina),percentage of polymorphic loci (56.3%-68.8%in A.sinensis and 43.8%-56.3%in A.peregrina),and the observed heterozygosities (Ho=0.072-0.096 in A.sinensis and 0.070-0.107 in A.peregrina).The observed heterozygosities of the six populations were all noticeably lower than the Hardy-Weinberg expectations,mostly due to heterozygote deficiency in the populations of both species.The overall mean Fsr were small (FST=0.045,P＞0.05 in A.sinensis populations and 0.087,P＞0.05 in A.peregrina populations).Nei's genetic identity (I)estimates indicate low intraspecific (＞0.95)but higher interspecific (0.377-0.447)genetic diversity.The cluster analysis based on modified Roger's genetic distance (D)showed that the two species were divided into two branches.Both species are of limited dispersal capacity and a moderate geographical barrier might significantly restrict the gene exchange among populations,resulting in accumulation of local genetic differentiations.The A.sinensis populations used in this study were separated from each other by 155.2 to 271.4 km and the A.peregrina populations were separated from each other by 78.8 to 174.9 km with observable physical barriers.The aUozyme data showed only minimal genetic differentiation at population level,most likely as a result of gene exchange.It is reasoned that natural factors and human agricultural activities might have facilitated migration and dispersal for the two species.     

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     

Complement phenotypes in patients with psoriasis

Phenotype frequencies for the complement proteins C4A, C4B, Bf (factor B) and C3 were performed for 49 Caucasian patients with psoriasis. The C4*A6 allele was present in 26.6% of the patients as compared to 5.4% of healthy regional Caucasian controls, p less than 0.001, relative risk = 6.28. The C4*A6 allele is known to be in linkage disequilibrium with the HLA B17 allele and to produce a non-functional gene product when it occurs with the B17 allele. HLA B17 is known to be associated with psoriasis in many Caucasian populations. Additional findings in the present study were a significant reduction in the C4B*2 allele frequency, a non-significant increase in the Bf*F allele frequency and no difference for Bf or C3 phenotype frequencies in the patients with psoriasis as compared to the controls.     

Patterns of social and geographical distribution of transferrin subtype polymorphism in India

Transferrin subtypes have been determined by isoelectric focussing of sera from 536 individuals belonging to 9 South Indian populations: Vaidic Brahmins and Vaysya from Andhra Pradesh; Havik Brahmin, Lingayat and Jenu Kuruba from Karnataka; Namboodri Brahmin, Ezhava and Urali from Kerala; and Kallan from Tamil Nadu. C1 and C2 alleles are present in all the populations, whereas C4 is totally lacking and D1 occurs only in 3 populations. The highest frequency of C1 gene (0.814) is found in Havik Brahmins while C2 shows highest incidence among the tribe Urali. C1 occurs in slightly higher frequencies among the Hindu castes (range 0.724-0.814) than the tribal populations (range 0.698-0.703). C2 is more common in the tribes (range 0.281-0.290) compared to the castes (range 0.186-0.269). Strikingly the C3 allele is absent in all the 3 Brahmin samples but is present in 3 non-Brahmin castes and a tribal population. An examination of all the available data on Tf subtypes in India reveals no clear-cut decreasing north-south gradient in C1 gene as suggested by Walter et al. (1983). Interestingly, however, the same is observed when tribal populations are considered separately. Among the castes, in fact, the opposite trend (increasing north to south) is seen. It is suggested that the basic postulate of Walter et al. (1983) will hold good only among the tribal populations of the country. The data do not fully support the observation of Kamboh and Kirk (1983) that C3 is a specific marker of European (Caucasian) populations.     

Variation at the Est3 locus and adaptability to organophosphorous compounds in Zaprionus indianus populations

Carboxylesterases are enzymes often associated with insect resistance to insecticides. The Est3 locus of Zaprionus indianus Gupta (Diptera: Drosophilidae) harbors four alleles that encode carboxylesterases with potentially detoxifying roles. In this study, we propose a model of resistance to insecticides in Z. indianus based on the adaptability of the Est3 locus inferred from the spread of its alleles over 27 generations in experimental populations, and their frequencies in field populations, which were either exposed or unexposed to the organophosphorous insecticide malathion. The increase in the frequency of this allele in experimental populations, and its high prevalence in field populations exposed to organophosphorous insecticides suggest that natural selection favors individuals with the Est3-3 allele. The low frequency of this allele in unexposed field populations, and the low productivity of Est3-3 homozygotes indicate that an adaptive cost is associated with this allele. The existence of a marker locus for insecticide resistance in Z. indianus makes it possible to use this species as a bioindicator for monitoring the excessive use of organophosphorous products and the emergence of resistance, and to devise strategies for the management of agricultural pests.     

PI and TF subtypes in Chuetas (Majorcan Jews).

PI and TF subtypes were studied in a sample of 137 individuals of the Chueta population. In addition to the PI*M alleles, PI*S, PI*Z, and PI*F were observed in the PI system. In the TF system no TF*B or TF*D alleles were found. PI results were compared with those of some Jewish and non-Jewish populations. The relatively high frequency of PI*S is indicative of a substantial Spanish influence. There are no previous data available on TF*C subtypes in Jews. The very low TF*C3 frequency in Chuetas (lower than in Spain) indicates that this allele may be extremely rare or absent in other Jewish populations.     

Nearly identical allelic distributions of xanthine dehydrogenase in two populations of Drosophila pseudoobscura

In a previous study, Keith (1983) showed by sequential gel electrophoresis of the esterase-5 protein in Drosophila pseudoobscura that a highly polymorphic locus with many alleles can have very similar frequency distributions in populations separated by 500 km. The present work studies another highly polymorphic locus, xanthine dehydrogenase, in the same California population samples, using the same technique to distinguish allelic classes. Twelve electromorphs were found in one population and 15 in the other. Both populations shared a single very frequent (approximately 60%) allele, as well as five other alleles in low but similar frequencies. In addition, each population had an array of unique alleles present only once in one population sample but absent in the other. A statistical test against the stationary distribution for neutral alleles shows that, if the populations are at equilibrium, then purifying selection is operating on xanthine dehydrogenase. The extremely close similarity in frequency distributions of the alleles between populations for both the xanthine dehydrogenase and esterase-5 loci, despite differences in allele frequency distribution between loci, strongly emphasizes the importance of migration in influencing genic diversity in these populations.     

The frequency and distribution of thiopurine S-methyltransferase alleles in south Iranian population

Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathiopurine. Variability in TPMT activity is mainly due to genetic polymorphism. The frequency of the four allelic variants of the TPMT gene, TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B (G460A) and TPMT*3C (A719G) were determined in an Iranian population from south of Iran (n = 500), using polymerase chain reaction (PCR)-RFLP and allele-specific PCR-based assays. Four hundred seventy four persons (94.8%) were homozygous for the wild type allele (TPMT*1/*1) and twenty five people were TPMT*1/*3C (5%). One patient was found to be heterozygous in terms TPMT*1 and *2 alleles with genotype of TPMT*1/*2 (0.2%). None of the participants had both defective alleles. The TPMT*3C and *2 were the only variant alleles observed in this population. The total frequency of variant alleles was 2.6% and the wild type allele frequency was 97.4%. The TPMT*3B and *3A alleles were not detected. Distributions of TPMT genotype and allele frequency in Iranian populations are different from the genetic profile found among Caucasian or Asian populations. Our findings also revealed inter-ethnic differences in TPMT frequencies between different parts of Iran. This view may help clinicians to choose an appropriate strategy for thiopurine drugs and reduce adverse drug reactions such as bone marrow suppression.     

Allele frequency distribution of CYP2C9*2 and CYP2C9*3 polymorphisms in six Mexican populations

Allele frequency differences of functional CYP2C9 polymorphisms are responsible for some of the variation in drug response observed in human populations. The most relevant CYP2C9 functional variants are CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910). These polymorphisms show variation in allele frequencies among different population groups. The present study aimed to analyze these polymorphisms in 947 Mexican-Mestizo from Mexico City and 483 individuals from five indigenous Mexican populations: Nahua, Teenek, Tarahumara, Purepecha and Huichol. The CYP2C9*2 allele frequencies in the Mestizo, Nahua and Teenek populations were 0.051, 0.007 and 0.005, respectively. As for CYP2C9*3, the allelic frequencies in the Mestizo, Nahua and Teenek populations were 0.04, 0.005 and 0.005, respectively. The CYP2C9*2 and CYP2C9*3 alleles were not observed in the Tarahumara, Purepecha and Huichol populations. These findings are in agreement with previous studies reporting very low allele frequencies for these polymorphisms in American Indigenous populations.     

Patterns of Gene Variation in Central and Marginal Populations of DROSOPHILA ROBUSTA

The central and marginal populations of D. robusta differ greatly in the level of inversion polymorphism; the marginal populations are monomorphic or nearly so and the central populations are highly polymorphic. This paper presents the frequencies of alleles at forty gene loci in various populations of D. robusta, studied by electrophoresis of proteins and enzymes. Population samples were obtained from eight widely separated populations of D. robusta which included the central, the extreme marginal and the intervening populations between the center and the margins. We find that the proportion of polymorphic loci and average heterozygosity per individual is slightly higher in the marginal populations than the central populations. In D. robusta on an average, 39% of the loci are polymorphic and the average proportion of loci heterozygous per individual is 11%. A breakdown of loci in three categories, viz, hydrolytic enzymes and some other enzymes, larval proteins and glycolytic and Kreb's cycle enzymes, shows that in all populations the level of polymorphism is highest in the hydrolytic enzymes, intermediate in larval proteins and least in the glycolytic and Kreb's cycle enzymes. On the average, the proportion of loci heterozygous per individual for three groups of loci is: hydrolytic enzymes and others (.164), larval proteins (.115) and glycolytic and Kreb's cycle enzymes (.037). We also observe that in all populations the level of polymorphism on the X chromosome is far less than the expected 38%; in salivary gland cells the euchromatic length of the X chromosome is 38% of the entire genome. Lower levels of polymorphism for the X chromosome loci are explained due to low probability of balanced polymorphisms for the X-linked loci since the conditions for establishment of balanced polymorphism for X-linked loci are more restrictive than for the autosomal loci.-The polymorphic loci can be grouped according to pattern of allele frequencies in different populations as follows: (1) The allele frequencies are similar in all populations at the XDH, Pep-1 and Hex-1 loci. (2) The alleles at the Est-1, Est-2, Amy loci and the AP-4(1.0) and the LAP-1(.90) alleles show north south clinal change in frequency. (3) There is north south and east west differentiation at the Pt-5, Pt-8 and Pt-9 loci and the allele AP-4(.81). (4) Polymorphism at loci such as Fum, B.Ox, Hex-8, Pep-2 and Pep-3 are restricted to only one or two of the populations. (5) Allele frequencies at the MDH and ODH loci fluctuate between populations. (6) Allele frequencies at many polymorphic loci such as Est-1, Est-2, LAP-1, AP-4, Pt-5, Pt-8, Pt-9, Pt-16, MDH, Fum change clinally within a gene arrangement. The pattern of gene variation in D. robusta is very complex and cannot be easily explained due to migration of neutral alleles between once-isolated populations or to semi-isolation of neutral alleles. The observations of the pattern of allele variation in different populations, high levels of polymorphism in the marginal populations which have small population size and low levels of polymorphism of the X chromosome loci all support the argument in favor of balancing selection as the main mechanism for the maintenance of these polymorphisms. Environmental factors must play a role in the maintenance of a great deal of these polymorphisms, since we observe clinal allele frequency changes even within a given inversion type.