Kuldeep Bhatia

Distribution of ADH2 and ALDH2 genotypes in different populations

SummaryThe distribution of the human liver alcohol dehydrogenase, ADH2, and aldehyde dehydrogenase, ALDH2, genotypes in 21 different populations comprising Mongoloids, Caucasoids, and Negroids was determined by hybridization of the amplified genomic DNA with allele-specific oligonucleotide probes. Whereas the frequency of the ADH12allele was found to be relatively high in the Caucasoids, Mexican Mestizos, Brazilian Indios, Swedish Lapps, Papua New Guineans and Negroids, the frequency of the ADH22gene was considerably higher in the Mongoloids and Australian Aborigines. The atypical ALDH2 gene (ALDH22) was found to be extremely rare in Caucasoids, Negroids, Papua New Guineans, Australian Aborigines and Aurocanians (South Chile). In contrast, this mutant gene was found to be widely prevalent among the Mongoloids. Individuals possessing the abnormal ALDH2 gene show alcohol-related sensitivity responses (e.g. facial flushing), have the tendency not to be habitual drinkers, and apparently suffer less from alcoholism and alcohol-related liver disease.

Alpha-thalassemia in Papua New Guinea

SummaryA study of the distribution of α-thalassemia in Papua New Guinea (PNG) was carried out by DNA analysis. A total of 664 DNA samples were screened for α-thalassemia 2 and α-thalassemia 1 caused respectively by either deletion of one or both of the duplicated α-globin genes. α-Thalassemia 2 was detected in high frequencies in coastal and lowland regions where malaria has been holo- to hyperendemic but in low frequencies in non-malarious highland regions. The highest frequency was observed in the north coast of PNG. The distribution of α-thalassemia 2 seems to be in accordance with other conditions such as ovalocytosis and G6PD deficiency which are also prevalent in this population, suggesting that they may interact in protection against malaria. However, it appears to be negatively correlated with β-thalassemia and α-thalassemia 1, the latter being extremely rare in this population. Analysis of the types and subtypes of the single α-globin gene deletion revealed a predominance of the −α4.2 type in general, except in some regions in the south where the −α3.7 type is prevalent. The −α3.7 I subtype is the common form of the −α3.7 deletion in the PNG mainland. The −α3.7 III subtype, previously reported to be unique in Melanesians and Polynesians, was detected in an offshore island of PNG. However, this subtype is very rare in Melanesians from the PNG mainland.

Genetic studies of human apolipoproteins: XII. Population genetics of apolipoproteins in Papua New Guinea

The gene products of the apolipoprotein A‐I, A‐II, A‐IV, C‐II, C‐III, D, E and H loci have been screened by isoelectric focusing followed by immunoblotting from two Papua New Guinean populations, the Huli and the Pawaia. Only APO E and APO H revealed common polymorphisms. A putative unique A‐IV variant has been identified, but due to the lack of family data it is not characterized further. Three common APO H alleles were observed in both groups with comparable frequencies. But significantly different distributions of three APO E alleles were noted in the Huli and the Pawaia. The respective frequencies of the APO E*2, APO E*3, and APO E*4 alleles were 0.154, 0.356, and 0.490 in the Huli and 0.138, 0.603, and 0.259 in the Pawaia. A strikingly high frequency of the APO E*4 allele in Papua New Guinea may provide a useful insight into the studies of genetic and environmental interactions in controlling the cholesterol levels in the general population.

Linear growth of children in Papua New Guinea in relation to dietary, environmental and genetic factors

Linear growth rates in rural Papua New Guinea vary widely by environmental zone. The 1982/83 National Nutrition Survey was a stratified cluster sample survey including questions on diet and anthropometry of children under five years of age. Regression analyses including 25,022 children from this survey show that variation in stature by altitude and precipitation level can largely be accounted for by differences in the fat and protein contents of village diets. Differences in linear growth rate between children living on different landforms show less relationship with diet. Genetic distances based on Class I HLA gene frequencies were calculated for 29 populations. Population mean recumbent lengths were estimated adjusted for age, diet, and environmental variables. The differences between populations in these average lengths were calculated. No significant correlation was found between genetic distances and differences in length. Genetic differences between ancestral populations as tracked by the HLA system do not appear to be an important factor contributing to variation in linear growth of Papua New Guinean children.

Sequencing and population analysis of four novel HLA-DPA1 alleles

We determined the base sequences of the HLA-DPA1 gene from four B-lymphoblastoid cell lines (CB6B, LKT3, AMAI, and T7526) that showed distinct electrophoretic patterns of single-stranded polymerase chain reaction products of the HLA-DPA1 gene. The novel HLA-DPA1 alleles of CB6B, LKT3, AMAI, and T7526 were designated DPA1*02021, DPA1*02022, DPA1*0301, and DPA1*0401, respectively. Although there was only one base substitution between DPA1*02021 and DPA1*02022, the single-strand conformation polymorphism of these two alleles was clearly demonstrated by electrophoresis in a nondenaturing polyacrylamide gel containing 10% glycerol. In addition, we genotyped for the HLA-DPA1 gene of healthy unrelated Oriental individuals--i.e., 227 Japanese, 88 Papua New Guineans, and 41 Buyi-Chinese--to demonstrate the ethnic distribution of the HLA-DPA1 alleles.

Host genetic factors do not account for variation in parasite loads in Strongyloides fuelleborni kellyi

Previous work in Papua New Guinea has shown considerable variation in egg counts between different people infected with Strongyloides fuelleborni kellyi, although individual egg loads remained relatively constant over a 14-month period. Possible explanations include genetic predisposition, a surprising longevity of the worms, or external auto-infection. We have now analysed the pedigrees of 177 individuals for whom egg counts were available, and find no evidence for polygenic inheritance of factors related to egg counts. The use of genetic models postulating the segregation of a single unknown susceptibility gene did not enable us, using the data available, to distinguish between this hypothesis and environmental determination of egg counts; nor did we find any association between egg load and the class 1 HLA genotype of the host.

HLA-A,B,C and DR antigens in Asaro speakers of Papua New Guinea

The HLA profile of the Asaro speakers of Papua New Guinea exhibits restricted polymorphisms. Antigens like AW24, MT1, and MB1 were present in almost every individual assayed. A CW6-related antigen and a DR locus antigen FT19 (a split of DRW6), not previously found in Pacific populations, were observed in a significant number of individuals. Ancestral HLA-B,C haplotypic combinations, such as B13, CW4 and BW60,CW3, were frequently found. Preliminary evidence is provided for an association between BW62 and CW65 in this population. The observed distributions of multiple-locus heterozygosities are similar to those expected under the null hypothesis of linkage equilibrium. The results indicate that the Asaro, among other highland populations, have been isolated long enough for pre-existing linkage disequilibria at recombinational distances of 0.8% or more (such as occur with HLA-A,B and HLA-B,DR haplotypes) to have broken down.

Albumin - vitamin D-binding protein haplotypes in Asian-Pacific populations

SummaryWe have determined the various haplotypic combinations between alleles as well as restriction fragment length polymorphisms of two linked genetic markers, albumin and vitamin D-binding protein or group-specific component, in a number of Asian-Pacific populations. Using the partial maximum likelihood method, we constructed a phylogenetic network from the haplotype frequencies to assess relationships among the populations sampled. No systematic linkage disequilibrium was detected between most of the combinations, suggesting a lack of operation of any selection pressure at the two loci. The phylogenetic analysis confirmed the known interrelationships among various populations in the Asian-Pacific region. The Australian aborigines clustered closely with the non-Austronesian-speaking highlanders from Papua New Guinea, as expected. Similarly, the Austronesian-speaking Polynesians, Micronesians, and the Southeast Asians branched off together as a separate group. The position of the Austronesian-speaking Tolais from New Britain with respect to other populations from the Southwest Pacific was anomalous. The Tolais revealed a strong affinity with the Australian aborigines, which is inexplicable. The populations from China formed a tight cluster with other populations from the Asian-Pacific region. Genetic interrelationships of these populations with the white Australians were remote, which is in accordance with the known affinities of various human racial groups.