Hideo Matsumoto

Characteristics of Mongoloid and neighboring populations based on the genetic markers of human immunoglobulins

SummarySince the discovery in 1966 of the Gm ab3st gene, which characterizes Mongoloid populations, the distribution of allotypes of immunoglobulins (Gm) among Mongoloid populations scattered from Southeast Asia through East Asia to South America has been investigated, and the following conclusions can be drawn: 1. Mongoloid populations can be characterized by four Gm haplotypes, Gm ag, axg, ab3st, and afb1b3, and can be divided into two groups based on the analysis of genetic distances utilizing Gm haplotype frequency distributions: the first is a southern group characterized by a remarkably high frequency of Gm afb1b3 and a low frequency of Gm ag, and the second, a northern group characterized by a high frequency of both Gm ag and Gm ab3st but an extremely low frequency of Gm afb1b3. 2. Populations in China, mainly Han but including minority nationalities, show remarkable heterogeneity of Gm allotypes from north to south and contrast sharply to Korean and Japanese populations, which are considerably more homogenous with respect to these genetic markers. The center of dispersion of the Gm afb1b3 gene characterizing southern Mongoloids has been identified as the Guangxi and Yunnan area in the southwest of China. 3. The Gm ab3st gene, which is found with its the highest incidence among the northern Baikal Buriats, flows in all directions. However, this gene shows a precipitous drop from mainland China to Taiwan and Southeast Asia and from North to South America, although it is still found in high frequency among Eskimos, Koryaks, Yakuts, Tibetans, Olunchuns, Tungus, Koreans, Japanese, and Ainus. On the other hand, the gene was introduced into Huis, Uyghurs, Indians, Iranians, and spread as far as to include Hungarians and Sardinians in Italy. On the basis of these results, it is concluded that the Japanese race belongs to northern Mongoloids and that the origin of the Japanese race was in Siberia, and most likely in the Baikal area of the Soviet Union.

IgG heavy chain allotypes (Gm) in atrophic and goitrous thyroiditis.

We typed coded sera from 135 healthy controls, seventy‐six patients with autoimmne goitrous and seventy‐three with atrophic thyroiditis for IgG heavy chain markers (Gm). All subjects were Caucasian from Newfoundland. An increase in the Gm phenotype ag was found in the 149 patients with thyroiditis compared to controls (X12= 5.82, P <0.01); significance was, however, not maintained after correction for the number of variables tested. The difference in ag phenotype was more pronounced among the seventy‐three patients with atrophic thyroiditis (X12= 8.80 corrected P < 0.05). Because the haplotype ag was not significantly increased in this group, we conclude that homozygotes for Gm ag are at an increased risk of developing atrophic thyroiditis.

The patient with combined deficiency of neuraminidase and 21-hydroxylase

SummaryTo investigate the possibility that delection en bloc in the HLA region had caused the combined deficiency of neuraminidase and 21-hydroxylase in a female patient, genetic markers on the short arm of chromosome 6 were examined in the patient and her parents, and 21-hydroxylase genes of the patient were analyzed by the Southern blot technique. The affected “extended haplotype” identical by descent might have been recombined at two sites, between HLA-A and C and between HLA-DQ and GLO. This suggests that the neuraminidase gene is mapped between HLA-A and GLO. Southern blot analysis revealed the existence of two 21-hydroxylase genes, so that we found no evidence to support the possibility that deletion en bloc in the HLA class III region had caused the combined deficiency of neuraminidase and 21-hydroxylase.

Subtyping of factor B by agarose gel electrophoresis

Conventional agarose gel electrophoresis (AGE) in Tris/glycine/barbital buffer (TGVB) could classify the common allotype “F” of factor B (BF) into two kinds of subtypes (Fb1 and F). Analysis of mother‐child pairs in paternity cases confirmed inheritance of these suballeles in the same manner as other alleles at the BF locus. The gene frequencies were estimated at 0.0154 for BF*Fb 1 and 0.1492 for BF*F through the study of 325 unrelated individuals. After treatment of serum samples with zymosan, the polymorphic band of BFFb 1 appeared in the Ba fragment, migrating between those of BFF and BFS. A technique of immunoblotting could demonstrate the BF patterns after AGE. This study provides a simple method for the detection of the BF subtypes and their electrophoretic characterization.

Studies on the human immunoglobulin allotypes in five populations in the USSR.

SummarySerum samples obtained from a total of 664 individuals representing five populations (Koryaks, Northern Buriats, Southern Buriats, Mongols and Uralians) in the USSR were tested for Glm(a,z,x and f) and G3m(b0,b1,b3,b4,b5,s,t,g and u), and Km(l) allotypes. According to Gm patterns, the first four of these populations are characterized by the presence of four haplotypes, namely Gm a,z;g,u, Gm a,z,x;g,u, Gm a,z;b0,b3, b5,s,t and Gm a,f;b0,b1,b3,b4,b5,u which are characteristic of Mongoloid populations, whereas the Uralian population is characterized by three haplotypes, Gm a,z;g,u, Gm a,z,x;g,u, and Gm f;b0,b1,b3,b4,b5,u which are common to Caucasoids as well as the Gm a,z;b0,b3,b5,s,t haplotype typical of northern Mongoloid populations. Results obtained from the four Mongoloid populations in Siberia indicate clear genocline, extending from Kamchatka to Mongol in which the haplotype frequency of Gm a,z;g,u changes from 0.714 to 0.431 and that of the Gm a,f;b0,b1,b3,b4,b5,u haplotype from 0.031 to 0.231. On the other hand, the Gm a,z;b0,b3,b5,s,t haplotype is found in the highest incidence (0.307) among Buriats from north Baikal, a population considered to have the most prominent Mongoloid characters, and indicates a cline from the Baikal to east and to south. In contrast to the Gm system, no significant regional differences in the frequencies of the Km1 allele were observed among these different populations.

Distribution of Blood Groups in Korea

Eight populations in the southern part of the Korean peninsula were studied to elucidate their genetic structure and to understand the genetic relationships between them. For this purpose, several blood groups and other genetic markers were analyzed. In total, over 9,000 blood specimens were collected. About 2,000 specimens were tested for 9 blood groups. The gene frequencies were estimated as A = 0.2555, B = 0.2244, O = 0.5201, M = 0.5263, S = 0.0560, d = 0.0472, C = 0.6542, E = 0.3126, Fya = 0.9210, Jka = 0.4386, Dia = 0.0539, P1 = 0.1939, K = 0.0010, Le = 0.6866 and Se = 0.6311 in the total sample. A continuous variation was observed for the frequency of gene B.

The probability of parentage exclusion based on restriction fragment length polymorphisms

SummaryBased on restriction fragment length polymorphisms (RFLPs) reported in the Eighth International Workshop of Human Gene Mapping (HGM8) held in Helsinki, the probability of parentage exclusion was calculated and the result was compared with those currently obtained from blood groups, serum groups and biochemical markers among Japanese. RFLPs would be very promissing in use of forensic medicine as well as mutation study. The eight probes with the highest probability yielded a joint probability of parentage exclusion as 99.5%. Sex-linked RFLPs, especially DXY segments which share homologous regions in both X and Y chromosome, would be very efficient in paternity exclusion, while RFLPs on mitochondrial DNA would be effective in maternity exclusion in mutation study. Conventional formulae for autosomal as well as sex-linked gene and RFLPs on mitochondrial DNA were summarized.

The origin of the Japanese race based on genetic markers of immunoglobulin G

This review addresses the distribution of genetic markers of immunoglobulin G (Gm) among 130 Mongoloid populations in the world. These markers allowed the populations to be clearly divided into 2 groups, the northern and southern groups. The northern group is characterized by high frequencies of 2 marker genes, ag and ab3st, and an extremely low frequency of the marker gene afb1b3; and the southern group, in contrast, is indicated by a remarkably high frequency of afb1b3 and low frequencies of ag and ab3st. Based on the geographical distribution of the markers and gene flow of Gm ag and ab3st (northern Mongoloid marker genes) from northeast Asia to the Japanese archipelago, the Japanese population belongs basically to the northern Mongoloid group and is thus suggested to have originated in northeast Asia, most likely in the Baikal area of Siberia.

The genetic studies of familial amyloid polyneuropathy in the Arao district of Japan: II. Studies of genetic markers in blood

SummaryBlood samples from 21 patients with familial amyloid polyneuropathy (FAP) and 81 normal family members among 7 affected families in Arao were tested for 9 blood group systems, 8 serum polymorphic proteins, 12 red cell polymorphic enzymes, and HLA. One of the most important findings was the existence of two relatively rare variants, i.e., group specific component Gc*1A2 and phosphoglucomutase PGM1*7 in 3 families. This observation suggests that the three genealogically independent families may have a common ancester. Phenotype AB in the ABO blood group system, phenotype 1 in the haptoglobin system, and M2 gene in the protease inhibitor system were not seen, and phenotype Jk(a+b−) in the Kidd groups was found in only one patient. Whether these observations reflect the characteristics of FAP in the Arao district or that of FAP itself can not be determined from the present study. No phenotype attributable to Caucasians was found, hence the study provides no support for the hypothesis that the gene for FAP was introduced into Japan by the Portuguese.

A BF subtype “Fb1” is a marker gene of some mongoloid populations

SummaryA factor B subtype, BF*Fb1, was first detected in Japanese by using isoelectric focusing or agarose gel electrophoresis in Tris/glycine/Veronal buffer. Our previous studies suggested that BF*Fb1 may be characteristic of some of Mongoloid populations. To investigate further distribution of BF*Fb1, samples randomly collected from Japanese in Yonaguni island of Japan and Cambodian were tested. BF*Fb1 was not observed in a Cambodian population whereas in a Japanese population of Yonaguni island, BF*Fb1 occurred at a frequency five times as high as those in main islands of Japan. In paternity cases, a Korean family with three offsprings was shown to transmit BF*Fb1 from the accused man to one of the offsprings. These data strongly indicate that BF*Fb1 is a marker gene for some of Mongoloid populations.