Surveys in a number of European and American populations have found the frequency of occurrence of the heterozygotes for the gene for the dibucaine-resistant variant of cholinesterase (E.C.3.1.1.8) to be relatively constant. Similar surveys in Oriental population have shown low incidence of the same gene. This study done on the multi-racial population consisting of 3 major groups shows an absence of the gene for the dibucaine resistant variant of cholinesterase. This is supported by the clinical experience in the use of suxamethonium as a single dose in more than 25,000 individuals.
Three taxa of the malaria mosquito Anopheles balabacensis complex representing three geographical regions (Thailand, Peninsular Malaysia and Sabah) in Southeast Asia, were analysed for genetic variation at 15 gene-enzyme systems. The Sabah taxon was monomorphic for all the 15 gene-enzyme systems. Only two gene-enzyme systems (esterase and glucose phosphate isomerase) were variable in the Thailand and Peninsular Malaysia taxa. The average heterozygosity or gene diversity was 0.007 for the Thailand taxon and 0.028 for the Peninsular Malaysia (Perlis) taxon. There were no unique gene-enzyme markers in the three taxa studied. The average values of genetic identities (0.933-0.997) and genetic distances (0.003-0.069) indicate that these three taxa are of subspecific status.
1. A total of 8 samples from three natural populations and a laboratory strain of Aedes albopictus were analysed for glycerol-3-phosphate dehydrogenase phenotypes by means of horizontal starch-gel electrophoresis. 2. The electrophoretic phenotypes were governed by three codominant Gpd alleles. 3. There was low variability, with the heterozygosity in the variable samples ranging from 0.02 to 0.12. 4. The commonest allele in all the population samples was GpdB which encoded an electrophoretic band with intermediate mobility. 5. There was no temporal or spatial variation.
A Monte Carlo simulation based on the population structure of a small-scale human population, the Semai Senoi of Malaysia, has been developed to study the combined effects of group, kin, and individual selection. The population structure resembles D.S. Wilson's structured deme model in that local breeding populations (Semai settlements) are subdivided into trait groups (hamlets) that may be kin-structured and are not themselves demes. Additionally, settlement breeding populations are connected by two-dimensional stepping-stone migration approaching 30% per generation. Group and kin-structured group selection occur among hamlets the survivors of which then disperse to breed within the settlement population. Genetic drift is modeled by the process of hamlet formation; individual selection as a deterministic process, and stepping-stone migration as either random or kin-structured migrant groups. The mechanism for group selection is epidemics of infectious disease that can wipe out small hamlets particularly if most adults become sick and social life collapses. Genetic resistance to a disease is an individual attribute; however, hamlet groups with several resistant adults are less likely to disintegrate and experience high social mortality. A specific human gene, hemoglobin E, which confers resistance to malaria, is studied as an example of the process. The results of the simulations show that high genetic variance among hamlet groups may be generated by moderate degrees of kin-structuring. This strong microdifferentiation provides the potential for group selection. The effect of group selection in this case is rapid increase in gene frequencies among the total set of populations. In fact, group selection in concert with individual selection produced a faster rate of gene frequency increase among a set of 25 populations than the rate within a single unstructured population subject to deterministic individual selection. Such rapid evolution with plausible rates of extinction, individual selection, and migration and a population structure realistic in its general form, has implications for specific human polymorphisms such as hemoglobin variants and for the more general problem of the tempo of evolution as well.
Seven natural populations of Dacus dorsalis were analysed for phosphoglucomutase by means of horizontal starch-gel electrophoresis. The electrophoretic phenotypes were governed by four codominant Pgm alleles. The commonest allele in all the seven population samples was PgmB which encoded an electrophoretic band with intermediate mobility. The distributions of PGM phenotype were in accordance with Hardy-Weinberg expectations. There was geographic variation in the distribution of Pgm alleles.
The relative viabilities of homozygous and heterozygous karyotypes were measured by making crosses between strains ofD. ananassae homozygous for ST or inverted gene orders in the second and third chromosomes. The strains utilized during the present study originated from widely separated localities in India, Kuala Lumpur and Kota Kinabaru, Malaysia and Chian Mai, Thailand. The presence of heterosis in many interpopulation crosses is evident from the results which show that the inversion heterozygotes formed by chromosomes coming from distant populations exhibit heterosis. On the other hand, heterosis is absent in two intrapopulation crosses. Thus the present results provide evidence that heterozygosis for many genes and gene complexes does produce high fitness without previous selectional coadaptation.
The Indian rubber estate workers in Negri Sembilan, Malaysia, who originated from Orissa in India were found to have a high frequency of Hb S (Joishy SK, Hassan K: Clin Res 28:280, 1980). Unlike the usually severe clinical picture of sickle cell anemia seen in African and American blacks, the clinical picture of the disease in this population was mild and many have reached old age. We studied the leukocyte DNA of 12 patients with sickle cell anemia, ranging in age from 4 to 61 years and 30 sickle cell trait carriers, ranging in age from 7 to 63 years, for the presence of alpha-globin gene deletions by gene mapping according to Southern (Southern EM: J Mol Biol 98:503, 1975), using alpha- and zeta-globin gene probes obtained by nick translation of the alpha- and zeta-globin genes cloned into plasmid. All 12 sickle cell anemia patients were found to have alpha-thalassemia2 (alpha-thal2), either in the homozygous or heterozygous condition. Of the Hb S trait carriers, six did not have alpha-thal2 or alpha-thal1 and 24 had alpha-thal2 (15 heterozygous, 9 homozygous). Seven of these Hb S trait carriers with alpha-thal2 had an additional gene abnormality. Five of them had a fast-moving Eco RI fragment 5.6 kb long that hybridized with zeta-specific probe but not with alpha-specific probe. An unusual DNA pattern of a different type was further found in the other two. Bgl II restriction analysis showed that the alpha-thal2 was mostly of the rightward deletion alpha-thal1 genotype. None of the sickle cell anemia patients and Hb S trait carriers had deletion type alpha-thal1. The sickle cell anemia patients had very high levels of Hb F and low levels of Hb A2. The Hb S trait carriers with alpha-thal2 had relatively low levels of Hb S.
Hereditary haemolytic anaemias, in particular, thalassaemia and the haemoglobinopathies, have been found to be a significant cause of hereditary haemolytic disease in West Malaysia. Theoretically 1 in 2500 marriages are between heterozygotes for beta-thalassaemia and 1 in 10,000 children can be expected to have thalassaemia major. An approach to the prevention of this disease would be public education and identification of carriers: to develop some approach to the identification and genetic counselling of beta-thalassaemia trait.
1. Population samples of Bactrocera albistrigata from Peninsular Malaysia were analyzed for 12 to 14 gene-enzyme systems comprising 15-18 loci. 2. Three loci, aMDH, PGD and PGM, were polymorphic. 3. Anodal malate dehydrogenase and phosphogluconate dehydrogenase were represented by two alleles each, while phosphoglucomutase was represented by three alleles. 4. Phosphoglucomutase had a higher heterozygosity than anodal malate dehydrogenase and phosphogluconate dehydrogenase. 5. B. albistrigata was characterized by low genetic variability, as measured by the proportion of polymorphic loci and heterozygosity.
This prospective study was performed to quantify glucose-6-phosphate dehydrogenase (G6PD) enzyme activity in deficient males and female heterozygotes. The methods used in the study were the fluorescent spot test, G6PD enzyme electrophoresis on cellulose acetate and quantitative assays. Forty-seven children who had been detected as spot screen deficient at birth were rescreened. Their first degree relatives were also included in the study. The mean enzyme activity of deficient males was 0.74 iu/g Hb (s.d. +/- 0.8), of female heterozygotes was 6.5 iu/g Hb (s.d. +/- 3.2) and of normal males was 12.1 iu/g Hb (s.d. +/- 3.5). The mean activity in deficient males was 6.1% of normal males. Most (35 of 47) of these fell into class 2 in Beutler's classification of G6PD variants. This indicates a population which may be susceptible to favism. Female heterozygotes had an intermediate enzyme activity with a wide scatter. Using a cut off point of enzyme activity of below 9.0 iu/g Hb gave sensitivity and specificity of 87% and 84% in detecting female heterozygotes. This group could be defined more accurately by combining quantitative assays with family studies.
A total of 103 beta thalassemia genes from 78 children (45 with Hb E/beta thalassemia, 8 with beta thalassemia heterozygotes, and 25 with homozygous beta thalassemia) were analyzed using dot-blot hybridization of the polymerase chain reaction-amplified DNA and direct DNA sequencing. Nine mutations were characterized in 98/103 (95%) of beta thalassemia alleles, of which six (a 4 bp deletion in codons 41-42, a G-C transition at position 5 of IVS-1, A-G transition at codon 19, an A-T transition at codon 17, an A-G transition at position -28 upstream of the beta globin gene, a G-T transition at position 1 of IVS-1), accounted for 92%. The spectrum of beta thalassemia mutations in Chinese Thai is similar to that reported among the Chinese from other parts of the world. The distribution of beta thalassemia mutations in Muslim Thai is similar to that reported among Malaysians. The most common beta thalassemia mutation in Thai and Chinese Thai patients is the frameshift mutation at codons 41-42, in comparison with the Muslim Thai in whom the G-C transition at position 5 of the IVS-1 mutation predominates. The heterogeneity of molecular defects causing beta thalassemia should aid in the planning of a prenatal diagnosis program for beta thalassemia in the South of Thailand.
Eggs of temperate Aedes albopictus populations are cold hardy and can diapause, but tropical populations are not cold hardy and cannot diapause. Heterozygotes possess intermediate diapause and cold hardiness. Males of a tropical strain from Malaysia with a distinctive genetic marker were released into an existing temperate population in East St. Louis, Illinois. Subsequent egg samples from the release site had genetic marker frequency of up to 24%. Reduced cold hardiness and decreased diapause incidence were also observed in the release site population. No such changes occurred at a nearby control site. The rank order of overwintering survival of eggs at the release site was: Aedes triseriatus > temperate Ae. albopictus > hybrid temperate/tropical Ae. albopictus > tropical Ae. albopictus. Eggs collected from the release population the next summer showed total absence of the genetic marker; presumably carriers were removed by the winter.
The clinical course of 18 patients with Wilson's disease is reported. There were 13 males and five females of whom one is Malay. The prevalence of Wilson's disease in Malaysia is probably the same as elsewhere. Being a genetic syndrome, the genetic carrier rate for Wilson's disease is probably lower amongst the Malays. At diagnosis, the clinical signs were predominantly hepatic in 10 patients, neurological in five patients with three asymptomatic cases. All patients were commenced on penicillamine but poor compliance was observed in many patients. Two patients defaulted follow-up and seven patients died. Out of the nine surviving patients, only four are well with no clinical symptoms.
The technique of isoenzyme electrophoresis was applied to Japanese wild populations of Taenia taeniaeformis (isolated from Norway rats) and three laboratory reared isolates (KRN isolated from a Malaysian Norway rat, BMM from a Belgian house mouse and ACR from a Japanese gray red-backed vole). The average heterozygosities of Japanese wild populations were fairly small and total genetic variability was 0.0499. The genetic make-up of T. taeniaeformis in Norway rats was rather uniform in the whole of Japan. In KRN isolate, each of all 10 loci examined possessed the allele which was predominant in Japanese wild populations. Similarly, each of 9 loci in BMM isolate possessed the same alleles, but one of 2 alleles at HK locus was different from that in the others. T. taeniaeformis parasitizing house mice and rats were considered to be genetically closely related to each other. In ACR isolate, 7 out of 10 loci possessed different alleles from those in the other populations. It was considered that ACR isolate was genetically distant and its phylogenetic origin in Japan should be different from worms parasitizing Norway rats.
The chromosome in situ suppression hybridization or chromosome painting technic was applied to confirm and eliminate the markers involving chromosome 21 segments using a chromosome 21 DNA library. The library ATCCLL21SNO2 was amplified, directly biotinylated using the polymerase chain reaction. The results demonstrated a translocation of chromosome 21 material on chromosome 2 and X and eliminate the origin of the marker. Thus, the technique provides an important tool to complement the conventional G-banding technic.
The spectrum of beta-thalassemia mutations in Malays in Singapore and Kelantan (Northeast Malaysia) was studied. Allele specific priming was used to determine the mutations in beta-carriers at -28, Codon 17, IVSI #1, IVSI #5, Codon 41-42 and IVSII #654 along the beta-globin gene. The most common structural hemoglobin variant in Southeast Asia, Hb E, was detected by DNA amplification with restriction enzyme (Mnl1) analysis. Direct genomic sequencing was carried out to detect the beta-mutations uncharacterized by allele-specific priming. The most prevalent beta-mutations in Singaporean Malays were IVSI #5 (45.83%) followed by Hb E (20.83%), codon 15 (12.5%) and IVSI #1 and IVSII #654 at 4.17% each. In contrast, the distribution of the beta-mutations in Kelantan Malays differed, with Hb E as the most common mutation (39.29%) followed by IVSI #5 (17.86%), codon 41-42 (14.29%), codon 19 (10.71%) and codon 17 (3.57%). The beta-mutations in Kelantan Malays follow closely the distribution of beta-mutations in Thais and Malays of Southern Thailand and Malays of West Malaysia. The AAC-->AGC base substitution in codon 19 has been detected only in these populations. The spectrum of beta-mutations in the Singaporean Malays is more similar to those reported in Indonesia with the beta-mutation at codon 15 (TGG-->TAG) present in both populations. The characterization of beta-mutations in Singaporean and Kelantan Malays will facilitate the establishment of effective prenatal diagnosis programs for beta-thalassemia major in this ethnic group.
Hemophilia B is an X-linked recessive disorder of the hemostasis involving a defective clotting factor IX. Amplification of the regions containing restriction fragment length polymorphisms (RFLP) can be achieved by the use of polymerase chain reaction (PCR). This paper describes the analysis of 2 RFLPs involving the Dde1 and Taq1 restriction sites within the factor IX gene in a family with hemophilia B. Digestion of the PCR products with Taq1 revealed a 163bp fragment in all the family members. This finding suggests the absence of restriction site for Taq1 enzyme. However, the Dde1 digest results in bands 369bp and 319bp segregated amongst the family members. The pattern of inheritance of the 369bp fragment in this family suggested that both the patient's mother and aunt are not carriers and that the patient's factor IX gene could have undergone a de novo mutation producing a defective factor IX gene responsible for the hemophilia B. This is supported by the fact that no family history of hemophilia B is indicated in the other male members within the family.
The allele frequencies for the apolipoprotein B (apo B) 5'-Ins/Del and 3'-VNTR polymorphisms varied significantly (p < 0.01) among Singaporeans of Chinese, Malay and Indian descent. We calculated the unbiased expected heterozygosities for the 5'-Ins/Del polymorphism as 0.3357, 0.1984 and 0.2418, and for the 3'-VNTR as 0.5980, 0.5260 and 0.6749, respectively, in the Chinese, Malays and Indians. Compared to heterozygosities reported for other populations, the Singaporeans differed from most Caucasians in having significantly lower values but were closely related to other non-Caucasians. Thirteen alleles, with a bimodal distribution, were observed at the 3'-VNTR polymorphic locus; the alleles occurring most frequently among the Chinese and Malays were of 35 or 53 repeats, and among the Indians, of 37 or 47 repeats. The Del allele was associated with elevated serum cholesterol (p = 0.023), LDL-cholesterol (LDL-C) (p = 0.001) in the Chinese, and apo B (p = 0.007) in the Indians. Likewise, the larger 3'-VNTR alleles (> 41 repeats) were associated with raised cholesterol (p = 0.018), LDL-C (p = 0.025), and triglyceride (p = 0.001) in the Chinese. The two polymorphisms were not in significant linkage disequilibrium (D = -0.0029, p = 0.494) in the three ethnic groups.