Incidence patterns indicated the prominent role of genetic factors in this type of cancer. A histocompatibility leukocyte antigen (HLA) profile of A2 and B-locus antigen, Singapore 2 (Sin 2), was identified. An association between these genes and increased risk for nasopharyngeal carcinoma (NPC), was confirmed. The risk was restricted to the "co-occurrence" of A2, B-Sin 2, suggesting that the genotype predisposing to the development of NPC was the A, B-Sin 2 haplotype. Similar associations were found to exist in Malaysian and Hong Kong Chinese so the A2, B-Sin 2 phenotype is a feature common to Asian Chinese in at least three locations. Preliminary HLA studies of medium NPC incidence in Tunisians and Malays indicated that patients with NPC of both ethnic types have altered HLA antigen profiles. If the findings of a locus-B antigen deficit in Tunisians and the role of A9 with B-locus antigens in Malays can be confirmed and clarified, the histocompatibility genetic hypothesis of NPC predisposition would be substantially strengthened.
Glucose phosphate isomerase (E.C. 126.96.36.199) and phosphoglucomutase (E.C. 188.8.131.52) were found to be polymorphic in a laboratory colony of Aedes albopictus. The glucose phosphate isomerase locus is represented by two alleles resulting in three genotypes, while the phosphoglucomutase locus is represented by at least five alleles giving rise to a total of 15 genotypes. The inheritance of these two enzymes is of the Mendelian type with codominant alleles. Present data indicate that these genes are not linked.Of 105 mosquitoes analysed for these two gene-enzyme systems, the frequencies for glucose phosphate isomerase alleles are Gpi (S)=0.68 and Gpi (F)=0.32, while the frequencies for phosphoglucomutase alleles are Pgm (A)=0.16, Pgm (B)=0.11, Pgm (C)=0.19, Pgm (D)=0.30 and Pgm (F)= 0.24. The frequencies of the three glucose phosphate isomerase genotypes are in accord with Hardy-Weinberg expectations (X 1 (2) =2.74). Similarly, the frequencies of the 15 phosphoglucomutase genotypes probably do not differ significantly from Hardy-Weinberg expectations (X 10 (2) = 18.45).
Clinical studies were carried out on mild Indian sickle cell anaemia in Malaysia, and genetic and fertility studies were carried out on 101 families with and without sickle-cell haemoglobin (Hb S). The Indian sickle cell anaemia patients reached adulthood, and pregnancies and deliveries were uneventful without blood transfusion. There was no foetal wastage and the number of children produced was not significantly different from that in families without Hb S. 28 Indian patients hospitalized with Plasmodium falciparum malaria infection were also examined for their beta S genotype. P. falciparum malaria infection occurred much more frequently in individuals without Hb S than in Hb S carriers.
Chromosome analysis on different breed types of water buffaloes (Bubalus bubalis) was undertaken to identify their karyotypes and to determine the pattern of chromosome segregation in crossbred water buffaloes. Altogether, 75 purebred and 198 crossbred buffaloes including 118 from Malaysia and 80 from the Philippines, were analyzed in this study. The diploid chromosome number of the swamp buffalo from both countries was 48 and that of the river buffalo was 50, while all F1 hybrids exhibited 49 chromosomes. The F2 hybrids consisted of three different karyotype categories (2n = 48, 2n = 49, and 2n = 50), whereas the backcrosses included two different karyotype categories each, with 2n = 48 and 2n = 49 in the three quarters swamp types and 2n = 49 and 2n = 50 in the three quarters river types. Chi-square tests on pooled data from Malaysia and the Philippines indicated that the distribution of different karyotype categories of F2 animals did not deviate significantly from the 1:2:1 ratio expected if only balanced gametes with 24 and 25 chromosomes were produced by the F1 hybrids. In the three quarters swamp and three quarters river types, the respective karyotypic categories were in ratios approximating 1:1. The distribution of chromosome categories among the F2 hybrids and backcrosses suggests that only genetically balanced gametes of the F1 hybrids are capable of producing viable F2 and backcross generations.
Following complete DNA characterisation patients with Hb H disease were assigned into two groups: deletional (alpha +/alpha o) and non deletional (HbCS/alpha o). Earlier studies have indicated that the group with (HbCS/alpha o) has more severe clinical problems. The serum malonyldialdehyde (MDA) levels, a secondary product of lipid peroxidation were within the normal range, though significantly higher levels of MDA were seen in the non-deletional type of Hb H disease when compared with the deletional type. Markedly low vitamin E levels were also seen in the former group. There were no significant differences in clinical severity may be attributed to an interplay of the accelerated destruction of damaged mature red blood cells secondary to the oxidative denaturation of Hb H and inclusion precipitation; higher levels of Hb H and more inclusion precipitation were seen in the group with (HbCS/alpha o). Low levels of vitamin E in the (HbCS/alpha o) group being due to its consumption in the neutralisation of free radicals formed with the oxidation of globin chains.
The distribution of restriction fragment length polymorphism (RFLP) at the BamH1 site of the beta-globin gene was investigated in the Chinese, Indian, and Malay race in Singapore. The sample comprised of 183 normal individuals and 35 beta-thalassemia carriers in which 13 were couples with at least one beta-major child. The results from this study indicate that BamH1 polymorphism will be informative in 22% of pregnancies at risk for beta-thalassemia major in Chinese, 19% in Malays and 7% in Indians. In prenatal diagnosis using BamH1 polymorphism for one beta-major affected family, the fetus was diagnosed to be normal or beta-carrier. The validity of BamH1 polymorphism in the exclusion of beta-thalassemia major was subsequently confirmed at birth by globin chain biosynthesis.
The ability to identify the occurrence of different resistance genotypes in field populations of mosquito is considered important for the purpose of optimising chemical control operations. The recent development of rapid microassays of enzymes responsible for resistance has provided a means for rapidly assessing the genetic background of target mosquito populations. This concept is the topic of investigation in this study. Non-specific esterase activity, which is responsible for the resistance to organophosphates in Malaysian Culex quinquefasciatus Say adults, was determined in 3 field populations from Kuala Lumpur City using rapid enzyme assay. The optical density results were used to estimate the genotypic frequencies of the populations. Subsequently, time-dependent changes in the various frequencies were determined. Such techniques allowed rapid assessment of resistance genotypes for decision-making and its possible use in insect control merits further investigation.
The distributions of the D1S80 alleles and genotypes in the Chinese, Malays and Indians in Singapore were determined by amplified fragment length polymorphism (AMP-FLP) analysis. The distributions of the observed genotypes for the three races conformed to Hardy-Weinberg expectations. The system was applied to 19 families whose paternity had been established by restriction fragment length polymorphism (RFLP) analysis. In all cases, Mendelian inheritance of the alleles at the D1S80 locus could be demonstrated. D1S80 typing on DNA recovered by differential extraction of forensic specimens which included vaginal swabs, urethral swabs and seminal stains yielded consistent results.
This study was conducted to evaluate the significance of genotype by environment (G x E) interactions for tropical poultry breeding. Three environmental conditions were considered: controlled normal-temperature (20 +/- 2 C, CN) and controlled high-temperature (32 C, CH) housing in Germany as well as natural open tropical housing in Malaysia (22 to 34 C, TO). Eighty-four sires were considered as genotypes. Their 5,352 progeny were tested simultaneously over three environments. For each sire, its part breeding value (BV) was estimated within each environment for each performance trait. Correlations between these BV for a pair of environments were used to estimate the magnitude of G x E interactions and the degree of relationship between them to demonstrate their implications on breeding strategies. Differences between observed and expected genetic correlations of BV for body weight, egg weight, egg number, egg mass, feed intake, and production efficiency as a fraction of the expected correlation were 5.1, 4.0, 36.7, 36.5, 17.7, and 31.6%, respectively, suggesting greater significance of G x E interactions for reproduction and production efficiency. The relationships between BV over the three environments were linear for most of the traits studied, but the coefficients of determination were dependent upon the magnitude of interactions involved. Relative efficiencies of indirect selection in CN or CH for performance in TO were also very low.
The HLA-DQ alpha genotype and allele frequencies in 130 Malays, 125 Chinese, and 137 Indians in the Malaysian population were determined using a commercial HLA-DQ alpha DNA amplification and typing kit which distinguishes 6 alleles (DQA1.1, DQA1.2, DQA1.3, DQA2, DQA3, and DQA4) and 21 possible genotypes at this locus. All 21 genotypes were encountered in the Malay and Indian samples, but DQA1.1,DQA1.3 and DQA2,DQA2 genotypes were absent in the Chinese sample. In all three ethnic groups, the numbers observed for the various DQ alpha genotypes were in accordance with those expected from Hardy-Weinberg equilibrium. The allele frequencies observed in these three groups were significantly different to allow them to be distinguished as distinct populations. For the Malays, Chinese, and Indians, heterozygosity values at this locus were 0.77, 0.77, and 0.83, respectively, and values of the power of discrimination were 0.91, 0.90, and 0.94, respectively. These population data will enable the HLA-DQ alpha locus to be used as a marker in forensic identity testing in Malaysia.
Members of the Semai group of Orang Asli ('aborigines') in peninsular Malaysia were examined for apolipoprotein E (apo E) variants in relation to plasma total cholesterol (TC), high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDLC), triglycerides (TG), apolipoprotein AI and apolipoprotein B (apo B). The e2 and e4 alleles were found to be higher than in most other groups as reported. The sample as a whole was normotriglyceridaemic (mean plasma TG, 1.5 mmol/l) and very markedly hypocholesterolaemic (mean plasma TC 1.7 mmol/l). The distribution of apo E variants was not related to any of the plasma lipids or apolipoprotein fractions using results from all subjects, but if a distinctly hypertriglyceridaemic sub-section was omitted (TG > 1.7 mmol/l) then apo E variants were determinants of plasma TC, LDLC, and apo B concentrations, the lower values of these being associated with the 2-2 and 2-3 genotypes, and the higher with 3-4, and 4-4.
Glutathione S-transferase-theta (GSTT1) is subject to a genetic polymorphism where approximately 50% of a Caucasian population are homozygous for the null allele. Because of the possible association of the polymorphism with increased cancer risk in individuals, we genotyped by polymerase chain reaction 187 normal Chinese, 167 normal Malays and 152 normal Indians from Singapore and Malaysia. The proportion of Chinese, Malays and Indians with the null genotype were 58%, 38% and 16% respectively and mirrored previously reported frequencies of the GSTM1 null genotype in these populations. The frequency of the combined GSTM1 and GSTT1 null genotypes among Chinese, Malays and Indians were 37%, 22% and 5% respectively. The similarity with predicted frequencies indicated no interaction between the two genetic polymorphisms.
Several xenobiotic metabolizing enzymes, including CYP1A1, NAT2 and GSTM1, are subject to genetic polymorphisms. Because these enzymes are important for the detoxification and/or bioactivation of drugs and carcinogens, these polymorphisms have important implications in therapeutics and cancer susceptibility. The distributions of CYP1A1, NAT2 and GSTM1 genotype frequencies in unrelated individuals of the Indian (n = 139) and Malay (n = 146) populations were characterized by the polymerase chain reaction. The respective allelic frequencies of wild-type and mutant alleles of CYP1A1 were 0.82 and 0.18 for the Indians, and 0.69 and 0.31 for the Malays. The frequencies of wild-type, M1, M2 and M3 of NAT2 among Indians were 0.44, 0.20, 0.32 and 0.04 respectively. The corresponding NAT2 allelic frequencies in Malays were 0.41, 0.12, 0.38 and 0.09. The GSTM1*A allele could not be amplified in 33.1% of Indians and 61.6% of Malays. At least one GSTM1*B allele was detected in 7.2% and 7.5% of the respective populations. The allelic frequencies of CYP1A1, NAT2 and GSTM1 among Malays are similar to previously reported frequencies among Chinese in the region. These findings will be of importance in the determination of cancer risks in these populations.
It is known that alpha1-antitrypsin deficiency is associated with emphysema in adults and liver cirrhosis in neonates. The phenotypes PiZZ and PiSZ are considered to be high risk groups. alpha1-antitrypsin deficiency is one of the most common lethal congenital disorders in Europe and the USA, occurring in approximately 1 in 2,000 caucasians of North European descent. Studies in Malaysia have found that the phenotypes PiZ and PiS are present in our population. Out of 950 samples analyzed, it was found that 10 samples were shown to be apparently Z homozygous phenotype. The phenotype is determined by high resolution isoelectrofocusing on an ultra-thin polyacrylamide gel embedded with narrow range Pi phamarlyte. The isoelectrofocused bands are confirmed by immunofixation and the plasma alpha1-antitrypsin levels determined by electroimmunoassay. The abnormal phenotypes are further confirmed by polymerase chain reaction using allele specific oligonucleotides.
Previous surveys of the prevalences of genotypes of hepatitis C virus (HCV) in different populations have often used genotyping assays based upon analysis of amplified sequences from the 5' noncoding region (5'NCR), such as restriction fragment length polymorphism (RFLP) or hybridization with type-specific probes (e.g., InnoLipa). Although highly conserved, this region contains several type-specific nucleotide polymorphisms that allow major genotypes 1 to 6 to be reliably identified. Recently, however, novel HCV variants found in Vietnam and Thailand that are distantly related to the type 6a genotype (type 6 group) by phylogenetic analysis of coding regions of the genome often have sequences in the 5'NCR that are similar or identical to those of type 1 and could therefore not be identified by an assay of sequences in this region. We developed a new genotyping assay based upon RFLP of sequences amplified from the more variable core region to investigate their distribution elsewhere in southeast (SE) Asia. Among 108 samples from blood donors in seven areas that were identified as type 1 by RFLP in the 5'NCR, type 6 group variants were found in Thailand (7 from 28 samples originally identified as type 1) and Burma (Myanmar) (1 of 3) but were not found in Hong Kong (n = 43), Macau (n = 8), Taiwan (n = 6), Singapore (n = 2), or Malaysia (n = 18). Although this small survey suggests a relatively limited distribution for type 6 group variants in SE Asia, larger studies will be required to explore their distribution in other geographical regions and the extent to which their presence would limit the practical usefulness of 5'NCR-based genotyping assays for clinical or epidemiological purposes.