病理性近视的家系研究

为了探讨我国病理性近视的遗传模式,对90个病理性近视大家系进行了分离分析。简单分离分析采用先验法和SEGRAN-B软件,进行拟合优度卡方检验,比较实际分离比与理论分离比的符合程度;复合分离分析运用SAGE-REGD软件进行孟德尔遗传模型(主基因、显性、隐性、共显性)和非孟德尔遗传模型(非传递、环境、一般)的拟合。结果显示,婚配类型为A*N的家系符合常染色体显性遗传,散发概率为13．8％,婚配类型为N*N的家系符合常染色体隐性遗传,散发概率为16．3％,但常染色体显性遗传不能除外,复合分离分析接受孟德尔遗传的显性、隐性、共显性和主基因模型,共显性模型的可能性最大,基因频率为0．21442999。因此,我国病理性近视存在常染色体显性和隐性遗传模式,并有一定比例的散发病例,具有遗传异质性。     

The plasminogen polymorphism in South African Negro populations: genetics and anthropogenetics

Summary Genetic polymorphism of human plasminogen (PLG) was investigated in 1252 unrelated individuals from eight South African Bantu-speaking Negro tribes. PLG phenotypes were determined by isoelectric focusing (pH 3.5–9.5 and 5–8 gradients) of neuraminidase-treated samples and subsequent detection by caseinolytic overlay or immunoblotting with specific antibody. No significant difference in the distribution of PLG alleles among the eight ethnic groups was observed. The combined allele frequencies of the common alleles in South African Negroes were 0.6977 for PLG*A, 0.2736 for PLG*B. In addition, six rare alleles were seen: PLG*A3, *A1, *M2, *B1, *B2, *B3. The rare variant PLG*B2 was proven to segregate by autosomal Mendelian inheritance in a family. The combined frequency for the rare alleles was 0.0287. The distribution of phenotypes in the total population sample was found to be in Hardy-Weinberg equilibrium. A striking difference in PLG allele distribution between Negroes from South Africa and published Negroid frequencies from North America could be observed. This difference was also seen in comparison with Mongoloid populations; in contrast, PLG frequencies for South African Negroes were similar or almost identical to known Caucasoid distributions.     

Genetic polymorphism of human factor H (beta 1H globulin)

Polyacrylamide gel isoelectric focusing (PAGIEF) of EDTA plasma and neuraminidase-treated plasma samples at pH 3.5-9.5 containing 8.0 M urea followed by an electroblotting with enzyme immunoassay was applied for the detection of factor H (HF) phenotypes in 536 unrelated Japanese blood donors living in Tokyo. In the major cathodal components, phenotypes of HF were classified into three common and five rare patterns, and these were considered to be controlled by two common and two rare alleles. The data suggest that the HF*Q0 allele also exists in the Japanese population. Family studies confirm the hypothesis that the HF polymorphism is controlled by autosomal codominant Mendelian inheritance.     

Electrophoretic variants of blood proteins in Japanese

Summary A total of 15,387 individuals living in Hiroshima and Nagasaki, of whom 10,864 are unrelated, were examined for erythrocyte triosephosphate isomerase (TPI) by starch gel electrophoresis using TEMM buffer, pH 7.4. Four kinds of new variants, one having a cathodal migration and three having anodal migrations, were encountered in this population. These variants were further characterized by starch gel electrophoresis using tris-EDTA buffer, pH 9.3, and isoelectric focusing. An anodally migrating allozyme TPI 2_HR1 exhibited markedly decreased enzyme activity, as evaluated by the staining intensity of the variant bands. The level of TPI activity in erythrocytes from this individual with the phenotype TPI 1-2_HR1 was about 60% of the normal mean. Family studies confirmed the genetic nature of all the variants.     

Two new Bf S subtypes revealed by isoelectric focusing and immunofixation

Summary The genetic types of the properdin factor B were analyzed by isoelectric focusing on polyacrylamide gels and subsequent immunofixation. Sera from 516 unrelated, healthy individuals from Southern Germany were examined. Two new subtypes of the Bf*S allele were observed. They were provisionally named Bf*Sb1 and Bf*Sb2 (b = basic), since the position of their bands is located slightly towards the cathode. Whereas Bf Sb2 has, thus far, been found only in a single individual, Bf Sb1 was found in five unrelated persons and in a mother and her child indicating a simple codominant mode of inheritance. The combined frequency of the Bf*Sb alleles was calculated to be 0.0067.     

Formal and population genetics of F13A and FUCA1 polymorphisms in northern Portugal

Subunit A of coagulation factor XIII (F13A) and alpha-L-fucosidase (FUCA1) polymorphisms were studied in unrelated healthy blood donors from northern Portugal. The gene frequencies found were: F13A*2 = 0.241 and FUCA1*2 = 0.308. Segregation analysis in mother/child pairs and nuclear families confirmed the previously described modes of inheritance for F13A and FUCA1, and no evidence for silent genes was found.     

Gc types in western Japan: report of a new variant Gc 1C35

Gc types were examined in a total of 1,000 unrelated Japanese individuals from Western Japan. By isoelectric focusing the six common subtypes and several rare types were observed. In addition, a new variant with a mobility between the Gc 1S and 1C2 was identified in 2 individuals. A family investigation confirmed the inheritance of the corresponding allele Gc* 1C35.     

Genetic mechanism of blood group (ABO)-expression

It has generally been believed that human blood group ABO is controlled by allelic ABO genes. However, this hypothesis has not yet been experimentally proven, and other possibilities such as the non-allelic gene model and the regulatory gene model for ABO locus have also been proposed. The genetic mechanisms of many unusual blood group expressions remain unanswered. Purification of human blood group N-acetylgalactosyltransferase (A-enzyme) which synthesizes A-substance, and blood group galactosyltransferase which is responsible for synthesis of B-substance, allows us to resolve these problems from an immuno-biochemical approach. It was found that rabbit antibody against-A-enzyme completely neutralized not only A-enzyme but also B-enzyme activity. Moreover, plasma from blood type O subjects contained an enzymatically inactive but immunologically cross-reactive material (CRM). Plasma from heterozygous AO and BO subjects also contained CRM, but plasma from homozygous AA and BB subjects did not contain CRM. These facts led us to conclude that the ABO genes are allelic in the strict sense, refuting other genetic models for ABO locus. Genotypes of phenotype A and B subjects can be unequivocally determined by examining the presence or absence of CRM in their plasma. Mechanism of the unusual blood group inheritance of Cis-AB (i.e., AB and/or O childbirth from AB X O parent) was elucidated by examining properties of the A and B enzymes, CRM in their plasma, and separation of active enzymes and CRM by affinity chromatography. It became clear that Cis-AB expressions in one family was due to unequal chromosomal crossing-over producing a single chromosome with the genes for A and B enzymes. In contrast, in the other two unrelated families, the Cis-AB expression was due to a structural mutation in A or B gene producing a single abnormal enzyme which was capable of transferring both GalNAc and Gal to H-substance. Mechanism of very weak B expression in a family with A1Bm character was studied. Plasma enzyme activity and kinetic characteristics of B-enzyme from the subjects was not different from that of normal. However, the A1Bm red cells contained a large amount of unoccupied H-sites which can be galactosylated in vitro and become B active. Examination of membrane components by isoelectric focussing revealed that blood group components of the A1Bm membranes were distinctively different from that of the usual membranes. Consequently, the weak B expression is not due to direct mutation of ABO locus, but due to a secondary consequence of genetic abnormality of a membrane component (or components) associated with blood group substances.     

Amino acid substitution and chemical characterization of a Japanese variant of carbonic anhydrase I: CA I Hiroshima-1 (86 Asp → Gly)

An electrophoretic variant of red cell carbonic anhydrase I, designated CA I Hiroshima-1, has been observed in 12 apparently unrelated individuals during a survey of 13,019 individuals from the cities of Hiroshima and Nagasaki, Japan. Analyses of tryptic and chymotryptic peptide patterns of this CA I variant purified from 8 of the 12 individuals revealed the same altered peptides in each case. Examination of the amino acid sequence of an altered tryptic peptide purified from one of the variants showed that the aspartic acid residue at position 86 was replaced by a glycine residue. Thermostability studies demonstrated that all samples of CA I Hiroshima-1 were less stable than normal CA I. The specific esterase (p-nitrophenyl acetate) activities of the normal and variant CA I isozymes were essentially the same. The difference spectra of the normal and variant enzymes were essentially the same. The isoelectric focusing patterns of CA I Hiroshima-1 showed a different pattern of minor bands to those produced by normal CA I. The relative amounts of the normal and variant enzymes purified from single heterozygous individuals were similar.This work was supported by U.S. Public Health Service grant GM-24681 and U.S. Department of Energy contract 2828 (to Dr. J. V. Neel).     

Ophthalmologic changes related to radiation exposure and age in adult health study sample, Hiroshima and Nagasaki

A 2-year ophthalmologic study of age and radiation-related ophthalmologic lesions among the atomic bomb survivors in Hiroshima and Nagasaki was conducted in 1978-80. The study sample in both cities was composed of all persons exposed to 100+ rad, their controls, and all other persons with a previous record of axial opacities or posterior subcapsular changes. Most of the losses were due to persons who refused to participate or for whom it was not possible to arrange for an ophthalmologic examination at the time of the regularly scheduled medical examination. It should be emphasized, however, that the loss of persons in both the control and the 100+ rad groups did not change systematically with increasing age by city. Increased lenticular opacities, other lens changes, and loss of visual acuity and accommodation occurred with increasing age in both exposed and control subjects as manifestations of the normal aging process. A highly significant excess risk for all age categories in the 300+ rad group in comparison to those in the control group was observed for both axial opacities and posterior subcapsular changes in Hiroshima, but not in Nagasaki. A stronger radiosensitive aging effect for persons who were under 15 years old at the time of the bombing (ATB) was observed for both axial opacities and posterior subcapsular changes in Hiroshima.     

The human serum paraoxonase/arylesterase polymorphism.

The heterozygous human serum paraoxonase phenotype can be clearly distinguished from both homozygous phenotypes on the basis of its distinctive ratio of paraoxonase to arylesterase activities. A trimodal distribution of the ratio values was found with 348 individual serum samples, measuring the ratio of paraoxonase activity (with 1 M NaCl in the assay) to arylesterase activity, using phenylacetate. The three modes corresponded to the three paraoxonase phenotypes, A, AB, and B (individual genotypes), and the expected Mendelian segregation of the trait was observed within families. The paraoxonase/arylesterase activity ratio showed codominant inheritance. We have defined the genetic locus determining the aromatic esterase (arylesterase) responsible for the polymorphic paraoxonase activity as esterase-A (ESA) and have designated the two common alleles at this locus by the symbols ESA*A and ESA*B. The frequency of the ESA*A allele was estimated to be .685, and that of the ESA*B allele, 0.315, in a sample population of unrelated Caucasians from the United States. We postulate that a single serum enzyme, with both paraoxonase and arylesterase activity, exists in two different isozymic forms with qualitatively different properties, and that paraoxon is a "discriminating" substrate (having a polymorphic distribution of activity) and phenylacetate is a "nondiscriminating" substrate for the two isozymes. Biochemical evidence for this interpretation includes the cosegregation of the degree of stimulation of paraoxonase activity by salt and paraoxonase/arylesterase activity ratio characteristics; the very high correlation between both the basal (non-salt stimulated) and salt-stimulated paraoxonase activities with arylesterase activity; and the finding that phenylacetate is an inhibitor for paraoxonase activities in both A and B types of enzyme.     

Enzyme activity and distribution of adenosine deaminase types in a population of central Italy

Blood samples from 718 unrelated individuals born in municipalities of the 'Alto Maceratese' region in central Italy were examined for adenosine deaminase (ADA). The allele frequencies for ADA*1 and ADA*2 were 92.48 and 7.45%, respectively. One case of the rare ADA 5-1 phenotype was observed. The observed phenotype distribution agreed well with the one expected assuming a Hardy-Weinberg equilibrium. Enzyme activity was measured in red blood cells from individuals with different phenotypes. The relationships between the enzyme activity of the phenotypes was found to be ADA 1 greater than ADA 2-1 greater than ADA 2 greater than ADA 5-1.     

Identification of base substitutions in ten types of rare variants of phosphoglucomutase-1 (PGM1) encountered in Japanese.

In a previous starch-gel electrophoresis study of erythrocyte phosphoglucomutase-1 (PGM1) in 23,095 Japanese from Hiroshima and Nagasaki, we detected 14 types of rare variant alleles. To determine sequence differences in these rare alleles, cell lines were established from peripheral B-lymphocytes from 24 unrelated individuals in whom nine types of rare variants are presumed to exist on the basis of earlier electrophoresis studies. cDNAs reverse transcribed from mRNAs extracted from these cell lines were amplified by polymerase chain reaction and sequences determined. Amino acid substitution types were deduced from each cDNA sequence. Although two individuals were reported to have an identical electromorph (PGM1 4HR3), sequence analysis revealed that alleles encoding these electromorphs possessed different base substitutions, and one was renamed PGM1 4HR4. As the amino acid substitution of ten different variants could be deduced by cDNA sequence in this study, the effect of each amino acid substitution on enzyme activity could be precisely simulated. The secondary structure of each variant predicted by computer simulations revealed that very decreased activity observed on PGM1 4HR2 protein was caused by significant secondary structure change introduced by the amino acid substitution. On the basis of the crystal structure, the amino acid substitutions of the ten types of rare variants seem to be outside the active center of this enzyme.     

Gamma-ray thermoluminescence measurements: a record of fallout deposition in Hiroshima?

In certain Hiroshima neighborhoods, radiation measurements using thermoluminescence dosimetry (TLD) exceed what can be explained by the initial gamma-ray doses and uncertainties from the Dosimetry System 2002 (DS02). This problem was not previously recognized as being isolated to certain parts of that city. The ratio between TLD measurements and DS02 dose calculations for gamma rays appear to grow larger than unity up to more than three with increasing ground range, but closer examination shows the excess TLD dose (0.1, 0.2, or possibly up to 0.8 Gray) is correlated with certain neighborhoods and could be due to radioactive fallout. At Nagasaki, the TLD measurements do not show this same excess, probably because there were no TLD measurements taken more than 800 m downwind (eastward) from the Nagasaki hypocenter, so that any small excess TLD dose was masked by larger initial gamma-ray doses of 25–80 Gray in the few downwind samples. The DS02 Report had noted many measurements lower than the DS02 calculation for several Nagasaki TLD samples, independent of ground range. This was explained as being the result of previously unaccounted urban shielding which was observed from Nagasaki pre-bomb aerial photos. However, the Hiroshima excess TLD dose issue was not resolved. If the excess TLD doses at Hiroshima are an indication of fallout, it may be possible to use additional TLD studies to make better estimates of the locations and radiation doses to survivors from the fallout after the bombings at both cities.     

Inheritance and linkage of allozymes in a Balkan endemic,Pinus peuce Griseb

This article presents a study of isozyme variation in Pinus peuce Griseb., a Balkan endemic. Among the enzyme systems studied, five were monomorphic and eight were polymorphic in at least one locus. The segregation analysis of the polymorphic loci were consistent with a Mendelian mode of inheritance. No significant deviation from the expected ratio was observed both at the individual and pooled segregation data levels. Segregation patterns were homogeneous across individuals. Two significant linkage groups were found in P. peuce: FEST-2:LAP-2 and 6PG-1:6PG-2, which correspond to the results obtained for other pine species.     

Esterase D polymorphism in a French-Canadian population

Summary Red blood cell esterase D (ESD) polymorphism was studied in a French-Canadian population from Quebec city, Canada, by means of high voltage electrophoresis on agarose gel followed, in heterozygotes for ESD1, by IEF to reveal the possible allele ESD^*5. Frequencies of the ESD alleles in 904 unrelated individuals were ESD^*1: 0.888, EDS^*2: 0.095 and ESD^*5: 0.017. The segregation pattern observed in 275 families confirmed a Mendelian inheritance of three autosomal alleles.     

Chemical characterization of a new Japanese variant of carbonic anhydrase I,CA INagasaki 1 (76 Arg→Gln)

A new inherited variant of carbonic anhydrase I (CA I), designated CA I_{Nagasaki 1} (CA I_{NGS 1}), was discovered during a survey of hemolysates from 5852 individuals from the cities of Hiroshima and Nagasaki in Japan. Analysis of the amino acid composition of a tryptic peptide from the CA I_{NGS 1} variant indicated that a glutaminyl residue was substituted for an arginyl residue at position 76. Heat degradation studies showed that the CA I_{NGS 1} variant was less stable than normal CA I. The CO₂ hydrase and esterase activities of the normal and variant carbonic anhydrases I, as well as the relative amounts of the two enzymes in heterozygotes, were similar.This work was supported in part by Contract E(11-1)-1552 with the Energy Research and Development Administration, Washington, D.C. (to J. V. Neel), and by U.S. Public Health Service Grant GM-24681.     

Genetic mechanism of cis-AB inheritance. I. A case associated with unequal chromosomal crossing over.

In contradiction to the general Mendelian inheritance of blood group ABO expression, the A and B characteristics are inherited together from one parent in the rare Cis-AB phenotype. Since the synthesis of blood group A and B substances are controlled by N-acetylgalactosoaminyltransferase (A-enzyme) and galactosyltransferase (B-enzyme), the genetic mechanism of Cis-AB expression may be elucidated by examining the characteristics of A- and B-enzymes in Cis-AB plasma. Biochemical study reveals that the examined Cis-AB plasma contains two separable enzyme components: one with kinetic properties similar to those of common A2-enzyme, but differing from A1-enzyme, and another with kinetic characteristics similar to those of common B-enzyme. Therefore, Cis-AB expression, at least in the case examined, is due to unequal crossing over, producing a chromosome with alleles for A2- and B-enzymes, rather than to a structural mutation in A or B alleles producing a single abnormal enzyme with bifunctional activity.     

Linkage relationships among 12 enzyme loci in cattle fever ticks of the genus Boophilus

Electrophoretic variation at 12 enzyme loci in cattle fever ticks were examined for mode of inheritance and linkage relationships. All variants exhibited codominant Mendelian inheritance, and PGI and GOT were sex-linked. Four pairs of enzyme loci were linked (PGI and GOT, ACON-A and alpha GPD, MDH-1 and LDH, and EST-3 and EST-4). Four additional enzyme loci (ACON-C, MDH-2, PEP, and PP) did not show linkage to any other locus tested, giving eight presumptive linkage groups that have enzyme markers in the genus Boophilus.