Investigations on the population genetics of the α1-antitrypsin polymorphism

Summary The results of Pi-typing on 2647 individuals from 9 populations are reported. Of the 17 phenotypes and 9 alleles described in literature, we found 12 phenotypes and 8 alleles. The population smaples differ characteristically in their allele frequencies. The allle Pi^M appears constantly in all populations tested with a frequency of more than 0.85. The alleles Pi^F (0.01–0.11), Pi^S (0.01–0.02) and Pi^Z (0.01–0.02) were also relatively frequent in all samples. All the other alleles remain below 0.01. A great increase in the number of Pi-variants was observed in the Central European area. The frequency of ₁-at variants in various populations is discussed.Supported by the Deutsche Forschungsgemeinschaft.Dedicated to Prof. W. Lehmann, Kiel, on his 65th birthday.     

Pi M4: An additional Pi M subtype

Summary The authors studied Pi polymorphism using the Separator isofocusing method with slight modification. A new Pi allele was observed. Family pedigrees confirmed co-dominant inheritance with other Pi alleles. According to the electrophoretic mobility of its isoprotein bands, and to its frequency (0.04) this new allele is considered as a fourth Pi ^M subtype: Pi ^M4.     

Alpha-1-antitrypsin types in five Chinese national minorities

Summary The frequencies of alpha-1-antitrypsin alleles were determined for five Chinese national minorities: Uigur, Korean, Mongolian, Chuang, and Li. PI^*S and PI^*Z alleles are not found in the five populations studied. PI^*ETOK allele is present in Korean, Mongolian, and Chuang populations, and Etokyo is a very common alpha-1-antitrypsin variant in Chinese. Other alleles which occur in more than one of the minorities are PI^*X (Mongolian and Chuang) and PI^*M4 (Korean and Uigur). The high frequency of PI^*M4 in the Uigur population suggests a probably Occidental origin of this nationality.     

Classification of α 1-antitrypsin (Pi) phenotypes by isoelectrofocusing

Summary Pi phenotypes have been determined by isoelectrofocusing in a sample of 538 healthy individuals from Southern Germany. Further subdivision of the common PiM phenotype is described. A procedure for the delineation of six common subtypes is presented. It is assumed that the six subtypes are determined by three alleles which are provisionally called Pi^Ma, Pi^Mb, and Pi^Mc. Their frequencies in this sample were 0.75, 0.06, and 0.15, respectively.Supported in part by INSERM, contract No. AT-FA-58     

Alpha1-antitrypsin: Physiology,genetics and pathology

Summary Alpha₁-antitrypsin (₁) is a glycoprotein in human serum that inhibits the enzymatic activity of trypsin and other proteolytic enzymes. Its concentration in normal serum is 200–250 mg/100 ml. In certain physiological and pathological situations, such as pregnancy, under contraceptive medication and during inflammation, the level of ₁-at is elevated. The physiological role of ₁ is not known, but the interaction with proteolytic enzymes from white blood cells is probably important. Electrophoretic techniques distinguish several phenotypes, which can be explained by the existence of several codominant alleles at one locus (probably the structural locus). Two alleles Pi^Z and Pi^S cause low concentrations of ₁-at in serum: the approximate concentrations of ₁-at for the different phenotypes are Z/Z 10%, M/Z 50–60%, S/S 60%, M/S 80%, where the level of 212 mg/100 ml found in the M/M phenotype is taken as 100%; thus the effect of these alleles on the ₁-at concentration is additive. Homozygosity for the Pi^Z allele is strongly associated with chronic obstructive lung disease and there is also an association of COPD and heterozygosity for the Pi^Z or Pi^S or both, but to a lesser degree.

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Zusammenfassung ₁-Antitrypsin (₁-at) ist ein Glykoprotein des menschlichen Serums. Es hemmt die enzymatische Aktivität von Trypsin und anderen proteolytischen Enzymen. Die Konzentration in normalem Serum beträgt etwa 200–250 mg/100 ml. Unter bestimmten physiologischen und pathologischen Bedingungen, z. B. während der Schwangerschaft, nach Verabreichung von Ovulationshemmern und während einer Infektion, ist der Serumspiegel des ₁-at erhöht. Die genaue physiologische Funktion des ₁-at ist unbekannt, wahrscheinlich ist aber die Hemmung von proteolytischen Enzymen aus Leukocyten von Bedeutung. Mit Hilfe elektrophoretischer Methoden kann man einige Phänotypen unterscheiden. Diese Phänotypen können durch mehrere codominante Allele an einem Locus, wahrscheinlich dem Strukturlocus, erklärt werden. Zwei Allele, Pi^Z und Pi^S, verursachen niedrige Konzentrationen von ₁ im Serum: Die ungefähren Serumkonzentrationen von ₁-at der verschiedenen Phänotypen sind: Z/Z 10%, M/Z 50–60%, S/S 60%, M/S 80%; die Konzentration von 212 mg/100 ml des M/M-Phänotyps ist hier gleich 100% gesetzt. Die Wirkung der verschiedenen Allele auf die ₁-at ist also additiv. Homozygotie für das Pi^Z-Allel ist statistisch signifikant mit chronisch obstruktivem Lungenemphysem assoziiert. Eine geringere, aber ebenfalls statistisch signifikante Assoziation mit chronisch obstruktivem Lungenemphysem besteht auch für die Heterozygotie Pi^M/Pi^Z und Pi^M/Pi^S oder nur für eine von beiden Heterozygotien.

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Recipient of a stipendium from Deutsche Forschungsgemeinschaft.     

The localization of rDNA in small,nucleolus-like structures in human diplotene oocyte nuclei

Summary Alpha-1-antitrypsin Pi phenotyping was performed by thin-layer isoelectric focusing on samples from 1653 healthy white blood donors. The variants were confirmed by the acid-starch gel technique and crossed immuno-electrophoresis, with complete agreement between the two methods. The allele frequencies in this population were PiM, 0.9019; PiS, 0.0713; PiZ, 0.0142; PiI, 0.0036; PiF, 0.0036; PiV, 0.0024. In addition, some rare phenotypes (MX, IS, LM) were noted. No difference was noted in the distribution of the variant alleles between males and females. The significance of the high frequency of the S allele is related to the ethnic origin of this population. The agreement of the results obtained by our technique and by acid-starch gel electrophoresis confirms the validity of Pi determination by thin-layer isoelectric focusing.     

Identification of Two Blast Resistance Genes in a Rice Variety, Digu

Blast, caused by Magnaporthe grisea is one of most serious diseases of rice worldwide. A Chinese local rice variety, Digu, with durable blast resistance, is one of the important resources for rice breeding for resistance to blast (M. grisea) in China. The objectives of the current study were to assess the identity of the resistance genes in Digu and to determine the chromosomal location by molecular marker tagging. Two susceptible varieties to blast, Lijiangxintuanheigu (LTH) and Jiangnanxiangnuo (JNXN), a number of different varieties, each containing one blast resistance gene, Pik^s, Pia, Pik, Pi‐b, Pi‐k^p, Pi‐ta², Pi‐ta, Pi‐z, Pi‐i, Pi‐k^m, Pi‐z^t, Pi‐t and Pi‐11, and the progeny populations from the crosses between Digu and each of these varieties were analysed with Chinese blast isolates. We found that the resistance of Digu to each of the two Chinese blast isolates, ZB13 and ZB15, were controlled by two single dominant genes, separately. The two genes are different from the known blast resistance genes and, therefore, designated as Pi‐d(t)1 and Pi‐d(t)2. By using bulked segregation method and molecular marker analysis in corresponding F₂ populations, Pi‐d(t)1 was located on chromosome 2 with a distance of 1.2 and 10.6 cM to restriction fragment length polymorphism (RFLP) markers G1314A and G45, respectively. And Pi‐d(t)2 was located on chromosome 6 with a distance of 3.2 and 3.4 cM to simple sequence repeat markers RM527 and RM3, respectively. We also developed a novel strategy of resistance gene analogue (RGA) assay with uneven polymerase chain reaction (PCR) to further tag the two genes and successfully identified two RGA markers, SPO01 and SPO03, which were co‐segregated toPi‐d(t)1 and Pi‐d(t)2, respectively, in their corresponding F₂ populations. These results provide essential information for further utilization of the Digu's blast resistance genes in rice disease resistance breeding and positional cloning of these genes.     

Alpha1-antitrypsin levels and electrophoretic patterns of several deficient phenotypes

Summary Two alleles, Pi^Z and Pi^S, are associated with lower than normal alpha₁-antitrypsin concentrations and lower trypsin inhibiting activities in human serum. The phenotypes that result due to heterozygosity or homozygosity for these alleles can be distinguished with electrophoretic procedures. The alpha₁-antitrypsin concentrations of several phenotypes overlap so that the phenotypes can be determined with certainty only by an electrophoretic procedure.

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Zusammenfassung Die zwei Allele Pi^Z and Pi^S führen zu subnormalen Konzentrationen von Alpha₁-Antitrypsin und niedrigen Trypsinhemmaktivitäten im menschlichen Serum. Die durch Hetero- und Homozygotie für diese Allele entstehenden Phänotypen können durch elektrophoretische Methoden unterschieden werden. Die Alpha₁-Antitrypsin-Konzentrationen der verschiedenen Phänotypen überlappen, so daß eine sichere Erkennung nur durch elektrophoretische Methoden möglich ist.

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This work was supported in part by Deutsche Forschungsgemeinschaft and Joachim Jungius-Gesellschaft der Wissenschaften Hamburg.     

Phosphoglucomutase (EC 2.7.5.1.) and adenylate kinase (EC 2.7.4.3.) typings in Koreans and Irish

Summary PGM₁ and AK phenotypes were determined in samples from Korea and Ireland. the frequencies of PGM ₁ ¹ genes amount to 0.916 in Koreans and 0.864 in Irish. AK¹ frequencies come to 0.933 in Koreans and 0.873 in Irish.Supported by the Deutsche Forschungsgemeinschaft.     

An excess of the Pi Sallele in dizygotic twins and their mothers

Summary A significant excess of the ₁ (protease inhibitor) Pi ^S allele has been found in 147 pairs of dizygotic (DZ) twins, but frequencies in 170 pairs of monozygotic (MZ) twins do not differ from those in a sample of 1007 blood donors. In 51 mothers of DZ twins the frequency of the Pi ^S allele was double than in the same sample of donors, but there was no corresponding increase in the fathers of DZ twins nor in the parents of MZ twins. In an independent sample of 66 mothers of twins of unknown zygosity, there was also a significant excess of Pi ^M Pi^S and Pi^M Pi^Z phenotypes, and this was particularly marked in the subsample of mothers of opposite-sex twin pairs. We speculate that lowered protease inhibitor levels in women carrying the Pi ^S allele may enhance sperm migration, increase the probability of multiple ovulation, or both.     

Polymorphism of α1-antitrypsin in a Portuguese population

Summary Serum Pi phenotypes were studied in 219 samples. The MM phenotype was the most common as in all other populations. The frequencies of Pi^S and Pi^Z were high considering other populations.Pi^F was not detected.This investigation was supported by a grant from Instituto de Alta Cultura (Project LMC.-10).     

Distribution of the electrophoretic variants of serum alpha1-antitrypsin in six species of the macaques

Individual variations of ₁-antitrypsin of the macaques were investigated by means of starch gel electrophoresis. The material comprised a total of 1,084 plasma samples taken from six species, namely,Macaca irus, mulatta, cyclopis, nemestrina, speciosa, andfuscata, including several geographical groups. At least ten phenotypes which were assumed in analogy to human Pi-system to be under genetic control of five codominant alleles tentatively denoted byPi _Mac ^{A, B, C, D, E} were identified. It was considered that these alleles are commonly possessed by different macaque species. A marked difference in the distribution of allele frequencies was found both within and between species groups. Several aspects of this new polymorphic variation in the macaques were discussed with special reference to the geographical distribution of the alleles and the origins of the Japanese macaque,M. fuscata. This study was carried out as part of the Special Project of the Japan-U.S. Cooperative Scientific Program: Blood Macromolecules and the Genetic Origins of the Japanese Macaques (Chief investigators:T. Miki andM. Goodman)     

Pseudocholinesterases and human red cell acid phosphatases in Koreans

Summary The authors reveal the results of pseudocholinesterase and human red cell acid phosphatase typings in a sample of 115 unrelated female Koreans aged from 20–30. No atypical pseudocholinesterase variants could be demonstrated. The frequencies of human red cell acid phosphatase alleles run up to: ph^A=0.231, ph^B=0.769, ph^C=0.000.This investigation was supported by the Deutsche Forschungsgemeinschaft.     

Studies on the population genetics of the ceruloplasmin polymorphism

Summary Phenotype and gene frequencies of the ceruloplasmin polymorphism are reported. In all populations considered here (Germans, Icelanders, Iranians, Pakistani, and Koreans) high frequencies of the allele Cp^B (0.978–0.996) could be observed, whilst the frequencies of the alleles Cp^A (0.003–0.013) and Cp^C (0.000–0.013) are very low.

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Zusammenfassung Die Verfasser berichten über Phänotypen-und Gen-Frequenzen des Coeruloplasmin-Polymorphismus. In allen untersuchten Populationen (Deutsche, Isländer, Iraner, Pakistani und Koreaner) konnten sehr hohe Frequenzen des Allels Cp^B beobachtet werden (0,978–0,996), während die Frequenzen der Allele Cp^A (0,003–0,013) und Cp^C (0,000–0,013) deutlich geringer sind.

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Supported by the Deutsche Forschungsgemeinschaft.     

Microsatellite profiles reveal an unexpected genetic relationship between Asian populations

Allelic frequencies for up to five short tandem repeat systems (HumTH01, HumVWA, HumF13B, HumCD4, HumD21S11) were analyzed in seven population samples from Asia using the polymerase chain reaction and gel electrophoresis. No deviations from Hardy-Weinberg equilibrium were observed. Two new alleles of the CD4 and TH01 loci were detected, and sequenced and their molecular structure is presented. A phylogenetic tree based on Thai, Han Chinese (from the northeast of China), Japanese, German and Ovambo allelic frequencies was constructed and demonstrates the close relationship of the Asian populations. Additionally, allelic frequency data for the VWA and TH01 systems were determined for the south Chinese minorities Bai, Dai and Qiang and for Koreans and compared with the above data. The Bai and Dai populations were clear outliers of the cluster of all other Asians, indicating an unexpected pattern of genetic heterogeneity of the Chinese nation. Two clusters of Asian populations could be established: the Koreans and Japanese together with the Han and Qiang Chinese, and, forming a separate cluster, the Bai and Dai populations. Received: 10 June 1997 / Accepted: 15 March 1998     

Fine mapping and DNA marker-assisted pyramiding of the three major genes for blast resistance in rice

Three major genes (Pi1, Piz-5 and Pita) for blast resistance on chromosomes 11, 6 and 12, respectively, were fine-mapped and closely linked RFLP markers identified. New markers for Pi1 and Pita were found that were flanking the genes. The three genes were pyramided using RFLP markers. A PCR-based SAP (sequence amplified polymorphism) marker was used to identify Piz-5 in the segregating population. The plants carrying the two- and three-gene combinations that were tested for resistance to leaf blast in the Philippines and India indicated that combinations including Piz-5 have enhanced resistance than when it is present alone. The genes from the pyramided lines are at present being deployed into agronomically superior ricevarieties by marker-aided selection (MAS). Received: 20 June 1997 / Accepted: 14 September 1999     

Identification of a null allele of cytochrome P450 3A7: CYP3A7 polymorphism in a Korean population

Cytochrome P450 3A7 (CYP3A7) is expressed in the human fetal liver and plays a role in the metabolism of hormones, drugs, and toxic compounds. Genetic variants of CYP3A7 are associated with serum estrone level, bone density, and hepatic CYP3A activity in adults. We analyzed the genetic variations of CYP3A7 in a Korean population. From direct sequencing of all exons and flanking regions of the CYP3A7 gene in 48 Koreans, we found five genetic variants, including three novel variants. One variant, a thymidine insertion in exon 2 (4011insT), causes premature termination of CYP3A7 translation, which may result in a null phenotype. The novel variant was assigned to the CYP3A7*3 allele by the CYP allele nomenclature committee. For further screen of this novel variant in other ethnic populations, we used pyrosequencing to analyze an additional 185 Koreans, 100 African Americans, 100 Caucasians, and 159 Vietnamese for the presence of this variant. The variant was not found in any other individuals, except for one Korean subject. The frequencies of two known functional alleles, CYP3A7*2 and CYP3A7*1C, were 26 and 0%, respectively, in Koreans. The frequencies of the functional CYP3A7 polymorphisms in Koreans were significantly different from those in Caucasians and African Americans. This is the first report of a null-type allele of the CYP3A7 gene. It also provides population-level genetic data on CYP3A7 in Koreans to reveal the wide ethnic variation in CYP3A7 polymorphism.     

Analysis of caprine pituitary specific transcription factor-1 gene polymorphism in indigenous Chinese goats

Since mutations on POU1F1 gene possibly resulted in deficiency of GH, PRL, TSH and POU1F1, this study revealed the polymorphism of goat POU1F1-AluI locus and analyzed the distribution of alleles on 13 indigenous Chinese goat breeds. The PCR-RFLP analysis showed the predominance of TT genotype and the frequencies of allele T varied from 0.757 to 0.976 in the analyzed populations (SBWC, Bo, XH and HM). Further study, distributions of genotypic and allelic frequencies at this locus were found to be significantly different among populations based on a χ²-test (P < 0.001), suggesting that the breed factor significantly affected the molecular genetic character of POU1F1 gene. The genetic diversity analysis revealed that Chinese indigenous populations had a wide spectrum of genetic diversity in goat POU1F1-AluI locus. However, the ANOVA analysis revealed no significant differences for gene homozygosty, gene heterozygosty, effective allele numbers and PIC (polymorphism information content) among meat, dairy and cashmere utility types (P > 0.05), suggesting that goat utility types had no significant effect on the spectrum of genetic diversity. X. Y. Lan and M. J. Li equally contributed to this work.     

Distribution of hereditary blood groups among indians in South America. VII. In Argentina

This seventh and last paper in a series on the distribution of blood groups among Indians in South America reports the findings among Amerinds in Argentina. Blood specimens were procured from putative full-bloods of the following tribes: 38 Diaguita (Calchaqui), 230 Mataco, 90 Chiriguano, 142 Choroti, 51 Toba, 120 Chané, 96 Chulupi (Ashluslay), and 178 Araucano (Mapuche). These 945 samples were tested for blood factors in the A-B-O, M-N-S-s, P, Rh-Hr, K-k, Lewis, Duffy, Kidd, and Diego systems. Serum samples were tested for haptoglobins and transferrins. Hemolysates prepared from whole blood were tested for hemoglobin types. The results are presented in tables as phenotype distribution and calculated allele frequencies. Locations of the populations from which blood samples were procured are shown on a map of North and Central Argentina. High frequencies are reported for the O allele. Allele frequencies are high also for M, s, R¹ (CDe), R² (cDE), k, Le^H and Fy. They are usually low or absent for alleles B, N, S, Mi^a, Vw, R^o (cDe), r (cde), K, Le¹, and fy. The Di allele ranged from 0.013 in the Araucano (Mapuche) to 0.192 in the Toba. Allele frequencies aberrant for Indians were observed more often in the Araucano (Mapuche) and Diaguita tribes, due probably to greater inflow of non-Indian genes into their gene pool and perhaps also to genetic drift in small inbred populations. Hp¹ allele frequencies varied from 0.43 in the Choroti to 0.80 in the Diaguita. All samples tested for transferrins except six contained the variant Tf C; the six were B₁ C present in samples from one Mataco and six Araucano persons. All the specimens tested electrophoretically for hemoglobin types contained only (A) as a major component.     

Serumprotein polymorphisms in Iran

Summary The results of a population genetic investigation on Iranians are given and compared to the results obtained on other populations from Southwestern and Southern Asia. Our total material from Iran comprises n=1020 nonrelated male and female individuals of different age. The following serum groups have been typed: Hp, Gc, Gm, and Inv. In general there exist no remarkable age or sex differences in the distribution of phenotypes and alleles (the only exception: sex differences in the distribution of the Gm (7)-phenotype). The regional distribution of phenotypes and alleles yield no marked differences, too, apart from the Invphenotypes, however. For the total material of Iran the following alleles frequencies could be calculated: Hp¹=0.3045, Hp²=0.6595, Gc²=0.3405; Gm¹=0.1780, Gm^1,2=0.0537, Gm^1,5=0.0632, Gm⁵=0.7051. The Gm (7)-phenotype turned out to be 36.6%; the Inv (1)-phenotype amounts to 25.6%. Comparing with other populations, especially Pakistani and Indian samples, some heterogeneity in the distribution of phenotypes and alleles within Southwestern and Southern Asia was to be demonstrated. Some distributional trends of alleles frequencies shall be mentioned here: the increase of Hp², Gc¹, and Gm¹ alleles from West towards East, and in the opposite direction the decrease of Hp¹, Gc², and Gm⁵ alleles. Selective acting forces are supposed to be most important factors for this. D77