Barry Boettcher

Mitochondrial Control-Region Sequence Variation in Aboriginal Australians

The mitochondrial D-loop hypervariable segment 1 (mt HVS1) between nucleotides 15997 and 16377 has been examined in aboriginal Australian people from the Darling River region of New South Wales (riverine) and from Yuendumu in central Australia (desert). Forty-seven unique HVS1 types were identified, varying at 49 nucleotide positions. Pairwise analysis by calculation of BEPPI (between population proportion index) reveals statistically significant structure in the populations, although some identical HVS1 types are seen in the two contrasting regions. mt HVS1 types may reflect more-ancient distributions than do linguistic diversity and other culturally distinguishing attributes. Comparison with sequences from five published global studies reveals that these Australians demonstrate greatest divergence from some Africans, least from Papua New Guinea highlanders, and only slightly more from some Pacific groups (Indonesian, Asian, Samoan, and coastal Papua New Guinea), although the HVS1 types vary at different nucleotide sites. Construction of a median network, displaying three main groups, suggests that several hypervariable nucleotide sites within the HVS1 are likely to have undergone mutation independently, making phylogenetic comparison with global samples by conventional methods difficult. Specific nucleotide-site variants are major separators in median networks constructed from Australian HVS1 types alone and for one global selection. The distribution of these, requiring extended study, suggests that they may be signatures of different groups of prehistoric colonizers into Australia, for which the time of colonization remains elusive.

Evolution in HLA-DRB1 and major histocompatibility complex class II haplotypes of Australian aborigines definition of a new DRB1 allele and distribution of DRB 1 gene frequencies

The distribution of HLA-DRB1 alleles was studied in Australian aborigines from different parts of Australia. There were significant differences in the frequencies of DRB1*0412, 1409, and 1410 between the Central Desert and Yuendumu populations and the previously reported Cape York and Kimberley aboriginal populations. A new DRB1 allele, DRB1*1414, present at low frequency in the Central Desert population, was identified. DRB1*1414 appears to be closely related to DRB1*1407 and is proposed to have arisen by intragenic recombination. A novel DR-DQ haplotype, DRB1*1402-DRB3*0101-DQA1*0501-DQB1*0402, was also identified. This haplotype may be ancestral to the DRB1*1409-DQB1*0402 haplotype present in these populations. The presence of alleles and haplotypes apparently confined to Australian aboriginal populations and differences in the distribution of these alleles in different populations suggests that evolution has occurred in the class II region in the period since colonization of Australia, an estimated 50,000 years ago.

An X-linked haplotype of Neandertal origin is present among all non-African populations

Recent work on the Neandertal genome has raised the possibility of admixture between Neandertals and the expanding population of Homo sapiens who left Africa between 80 and 50 Kya (thousand years ago) to colonize the rest of the world. Here, we provide evidence of a notable presence (9% overall) of a Neandertal-derived X chromosome segment among all contemporary human populations outside Africa. Our analysis of 6,092 X-chromosomes from all inhabited continents supports earlier contentions that a mosaic of lineages of different time depths and different geographic provenance could have contributed to the genetic constitution of modern humans. It indicates a very early admixture between expanding African migrants and Neandertals prior to or very early on the route of the out-of-Africa expansion that led to the successful colonization of the planet.

Sequence polymorphism in the mtDNA HV1 region in Japanese and Chinese

We investigated the nucleotide substitution and insertion/deletion polymorphism of the HV1 region in mtDNA by sequencing blood samples from 150 unrelated Japanese and 120 unrelated Chinese and revealed 108 sequence types from the Japanese group and 87 sequence types from the Chinese. Some substitutions were characteristic of East Asian populations as compared with data reported on Caucasian populations, and some were area-specific among East Asians. The level of genetic diversity and genetic identity revealed by this system was superior to that obtained by VNTR systems for nuclear DNA. These results show the usefulness of mtDNA sequencing in forensic examination for individual identification. We also found some sequence variations in the homopolymeric tract of cytosine (np16180-16194 in the Andersons reference sequence) that might suggest some hints regarding the mechanisms for and the development of heteroplasmic length variations in this tract.

Binding of Steroids to Human Spermatozoa and Its Possible Role in Contraception

The binding of steroids to human ejaculated spermatozoa and the effect of steroids bound to spermatozoa on sperm migration and motility in vitro was examined. A correlation between progestogens that bind to steroid-binding sites on human spermatozoa and progestogens that inhibit sperm migration was established. The results indicated that there is a direct and specific steroid effect on human spermatozoa, as some steroids such as progesterone, lynestrenol, and norethynodrel markedly inhibited sperm migration and motility, whereas other steroids such as estrone had no detectable effect on sperm migration and motility. The significance of these findings was discussed in relation to the contraceptive action of steroids applied directly to the lumen of the female genital tract.

Platelet antigen allele frequencies in Australian aboriginal and Caucasian populations.

Summary We have applied genotyping methods of PCR‐SSOP and PCR‐RFLP to three, bi‐allelic platelet specific antigen systems HPA‐1 (Pla), HPA‐3 (Bak) and HPA‐5 (Br). This combination of techniques offers flexibility for high volume or rapid typing. The phenotype and genotype frequencies of alleles from the three systems differ significantly between the Yuendumu Australian Aboriginals (Wailbri) and Australian Caucasians. The major differences are the very low frequencies of HPA‐1b and HPA‐3b in Yuendumu Aboriginals which are potentially relevant to platelet transfusion in patients of Australian Aboriginal descent.Abbreviations: HPA; human platelet‐specific antigen; NAIT, neonatal alloimmune thrombocytopenia; PTP, post transfusion purpura; PTR, platelet transfusion refractoriness; RFLP, restriction fragment length polymorphism; SSOP, sequence specific oligonucleotide probe; SSP, sequence specific primers.

Anticomplementary Activity in Human Semen and Its Possible Importance in Reproduction

ABSTRACT: We demonstrated anticomplementary activity on once‐washed human sperm, and in normal and vasectomized seminal plasmas. It was demonstrated to be a normal component of human semen. The origin of the activity is proposed to be the seminal plasma with sperm adsorption of activity. The properties of the seminal anticomplementary factor were characterized further, and the molecular size was shown to be less than 3500 daltons. Reduced anticomplementary activity was found to be associated significantly with abnormal semen profiles and infertility in males. The activity in seminal plasma was shown to have no effect on complement‐dependent sperm immobilizing antibodies in the serum of an infertile woman, implicating an effect on the post‐C3 components of the complement pathway. The inhibition of complement‐dependent haemolysis and the lack of inhibition of complement‐dependent sperm immobilization by the anticomplementary factor are considered in the implications of the role of seminal anticomplementary activity in reproduction.

Cytoplasmic influence on the expression of nuclear genes affecting life span in Drosophila melanogaster

In earlier studies we have found that the difference between short and long life spans of two inbred strains of Drosophila melanogaster is controlled by nuclear major genes. The present study has revealed a cytoplasmic factor that influences the expression of the nuclear longevity genes. The factor shows a typical maternal inheritance and is considered to be an extranuclear gene, such as mitochondrial DNA (chondriome). This paper marks the discovery of two basic forms of inheritance, nuclear and extra-nuclear, in the genetics of life span of D. melanogaster. These findings suggest that further studies, including genetic engineering, on longevity and aging might enable direct manipulation of these characters.

Relationship between genotypes of longevity genes and developmental speed in Drosophila melanogaster

Hatching time (the period between egg-laying and hatching) and emerging time were surveyed and their relationship with the adult life span was investigated. A relationship between emerging time and adult life span was clearly evident: early emergers were often long-lived. This relation is considered to have a genetic basis because all the larvae in a group were bred in the same culture bottle. Thus, the longevity genes involved also appear to have control over the rate of development. No significant relation was observed between hatching time and adult life span or between hatching time and emerging time. These results suggest that the function of the longevity genes begins at the larval or pupal stage before emergence, and that adult life spans differentiate at this time.

HLA class I alleles in Australian aborigines and their peptide binding profiles

The HLA system is under balancing selection. HLA alleles are maintained in populations by their divergent functions. The peptide binding profiles of HLA alleles may hold the key to a better understanding of HLA diversification and polymorphism maintenance. Long isolated Australian aboriginal populations provide a good model for these studies. The four HLA-A, seven B and five or six C alleles commonly detected in them represent the minimum class I repertoire carried by the founder group as well as the minimum class I polymorphism that needs to be maintained in these populations. All these alleles have a unique combination of the P2 and P9 anchor preferences indicating unique peptide binding profiles that have ‘earned’ their place in the minimum allele set. This study of Australian aborigines provides further insights into the mechanism of HLA evolution in general.