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The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all of the studied Aboriginal Australians descend from a single founding population that differentiated ~10-32 kya. We infer a population expansion in northeast Australia during the Holocene epoch (past 10,000 years) associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama-Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51-72 kya, following a single out-of-Africa dispersal, and subsequently admixed with archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.

The analysis of human population variation is an area of considerable interest in the forensic, medical genetics and anthropological fields. Several forensic single nucleotide polymorphism (SNP) assays provide ancestry-informative genotypes in sensitive tests designed to work with limited DNA samples, including a 34-SNP multiplex differentiating African, European and East Asian ancestries. Although assays capable of differentiating Oceanian ancestry at a global scale have become available, this study describes markers compiled specifically for differentiation of Oceanian populations. A sensitive multiplex assay, termed Pacifiplex, was developed and optimized in a small-scale test applicable to forensic analyses. The Pacifiplex assay comprises 29 ancestry-informative marker SNPs (AIM-SNPs) selected to complement the 34-plex test, that in a combined set distinguish Africans, Europeans, East Asians and Oceanians. Nine Pacific region study populations were genotyped with both SNP assays, then compared to four reference population groups from the HGDP-CEPH human diversity panel. STRUCTURE analyses estimated population cluster membership proportions that aligned with the patterns of variation suggested for each study population's currently inferred demographic histories. Aboriginal Taiwanese and Philippine samples indicated high East Asian ancestry components, Papua New Guinean and Aboriginal Australians samples were predominantly Oceanian, while other populations displayed cluster patterns explained by the distribution of divergence amongst Melanesians, Polynesians and Micronesians. Genotype data from Pacifiplex and 34-plex tests is particularly well suited to analysis of Australian Aboriginal populations and when combined with Y and mitochondrial DNA variation will provide a powerful set of markers for ancestry inference applied to modern Australian demographic profiles. On a broader geographic scale, Pacifiplex adds highly informative data for inferring the ancestry of individuals from Oceanian populations. The sensitivity of Pacifiplex enabled successful genotyping of population samples from 50-year-old serum samples obtained from several Oceanian regions that would otherwise be unlikely to produce useful population data. This indicates tests primarily developed for forensic ancestry analysis also provide an important contribution to studies of populations where useful samples are in limited supply., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Temporal bone shape has been shown to reflect molecular phylogenetic relationships among hominoids and offers significant morphological detail for distinguishing taxa. Although it is generally accepted that temporal bone shape, like other aspects of morphology, has an underlying genetic component, the relative influence of genetic and environmental factors is unclear. To determine the impact of genetic differentiation and environmental variation on temporal bone morphology, we used three-dimensional geometric morphometric techniques to evaluate temporal bone variation in 11 modern human populations. Population differences were investigated by discriminant function analysis, and the strength of the relationships between morphology, neutral molecular distance, geographic distribution, and environmental variables were assessed by matrix correlation comparisons. Significant differences were found in temporal bone shape among all populations, and classification rates using cross-validation were relatively high. Comparisons of morphological distances to molecular distances based on short tandem repeats (STRs) revealed a significant correlation between temporal bone shape and neutral molecular distance among Old World populations, but not when Native Americans were included. Further analyses suggested a similar pattern for morphological variation and geographic distribution. No significant correlations were found between temporal bone shape and environmental variables: temperature, annual rainfall, latitude, or altitude. Significant correlations were found between temporal bone size and both temperature and latitude, presumably reflecting Bergmann's rule. Thus, temporal bone morphology appears to partially follow an isolation by distance model of evolution among human populations, although levels of correlation show that a substantial component of variation is unexplained by factors considered here., ((c) 2007 Wiley-Liss, Inc.)

The pattern of dispersal of biologically and behaviorally modern human populations from their African origins to the rest of the occupied world between approximately 60,000 and 40,000 years ago is at present a topic of lively debate, centering principally on the issue of single versus multiple dispersals. Here I argue that the archaeological and genetic evidence points to a single successful dispersal event, which took genetically and culturally modern populations fairly rapidly across southern and southeastern Asia into Australasia, and with only a secondary and later dispersal into Europe.

Human physical pigmentation is determined by the type and amount of melanin and the process of pigmentation production probably involves more than 100 genes. A failure to synthesize melanin results in oculocutaneous albinism (OCA). A recently identified form of OCA results from mutations in the Membrane Associated Transporter Protein (MATP) gene. The role of MATP in human pigmentation is not clear. We investigated the role of two nonpathogenic nonsynonymous single nucleotide polymorphisms (SNPs) in the MATP gene to determine if they are associated with normal human skin, hair, and eye color variation. A total of 608 individuals from four different population groups (456 Caucasians, 31 Asians, 70 African-Americans, and 51 Australian Aborigines) were genotyped for c.814G>A (p.Glu272Lys) and c.1122C>G (p.Phe374Leu). Results indicate that the allele frequencies of both polymorphisms are significantly different between population groups. The two alleles, 374Leu and 272Lys, are significantly associated with dark hair, skin, and eye color in Caucasians. The odds ratios (ORs) of the LeuLeu genotype for black hair and olive skin are 25.63 and 28.65, respectively, and for the LysLys genotype are 43.23 and 8.27, respectively. The OR for eye color is lower at 3.48 for the LeuLeu and 6.57 for LysLys genotypes. This is the first report of this highly significant association of MATP polymorphisms with normal human pigmentation variation.

In this paper we critique two recent studies that have been claimed to disprove the Out of Africa hypothesis for modern human origins (Hawks et al., 2000; Wolpoff et al., 2001). We show that the test prediction employed by Hawks et al. (2000) and Wolpff et al. (2001) is not relevant to many versions of the Out of Africa hypothesis, and that the key specimens they used are problematic in terms of morphological representativeness. We also show that there are significant problems with the character state datasets employed in the studies. Lastly, we highlight evidence that the main method used in the studies (pairwise difference analysis) is not reliable when applied to the type of data employed by Hawks et al. (2000) and Wolpoff et al. (2001). In view of the foregoing, we contend that Hawks et al.'s (2000) and Wolpoff et al.'s (2001) claim to have disproved the Out of Africa hypothesis cannot be sustained.

Background and Purpose: Many investigators have approached ischemic stroke as a complex phenotype by dividing the ischemic stroke population into distinct subtypes. The purpose of this study was to review systematically the methods used to subtype ischemic stroke in recent genetic studies., Methods: The MEDLINE database was searched for articles pertaining to research on the genetics of human ischemic stroke published from January 2000 through January 2002. Abstracts and full-length reports were then sequentially screened to select articles pertaining to original case-control or cohort studies., Results: The initial search yielded 153 publications. Of 41 relevant articles, ischemic stroke was subtyped in 25 (61%). The most common standard subtyping system was the Cerebrovascular Classification of Diseases III system (9 articles). Of the subtyping systems used, 3 had previously published interrater reliability. The subtyping system was reported to have been prespecified in 1 study. Four articles reported using central adjudication. Two articles reported that the person doing the subtyping was blinded to genotype, and 2 reported that the person doing the genotyping was blinded to the patient's subtype status., Conclusions: When investigators subtyped ischemic stroke, they typically used either nonstandard classification systems or systems of undetermined reliability. Important methodological issues, including blinding and prespecification of the classification system, were rarely reported. Advances in methodology and scientific reporting standards would foster identification of subtype-specific genetic risk factors.

Two HFE gene mutations, C282Y and H63D, underlie the vast majority of cases of hereditary hemochromatosis. We performed a cross-sectional primary care-based study to determine the allele frequency of the C282Y and H63D mutations and the penetrance of each of the affected genotypes defined by their presence. Patients had previously undergone transferrin saturation (TS) testing. A total of 4865 unselected frozen serum samples were analyzed to determine serum ferritin (SF) levels. Genomic DNA isolated from these samples was analyzed for the C282Y and H63D HFE mutations. Homozygotes for each mutation and compound heterozygotes were evaluated to determine clinical penetrance. The allele frequency of C282Y was 0.0507 among Caucasian and 0.0067 among African Americans; that of H63D was 0.1512 and 0.0263, respectively. TS was > or =55% in 83% of individuals with C282Y/C282Y, 14.5% of C282Y/H63D, and 5% of H63D/H63D; SF was > or =300 microG/L in 42, 9, and 5% of these genotypes, respectively. None of the 12 C282Y homozygotes had cardiac dysfunction or hepatic cirrhosis. Only 9/129 (7%) individuals with the genotypes C282Y/H63D or H63D/H63D had a SF > or =300 microG/L; many had explanations other than iron overload that accounted for this increase. Thus, the prevalence of the common HFE mutations is the same in our population as previously described. TS screening would detect most C282Y homozygotes but not the other two genotypes. The penetrance of C282Y/C282Y is significant. The biochemical penetrance of H63D/H63D and C282Y/H63D is modest and the clinical penetrance is low.

Background: Anecdotal evidence suggests that people from non-Anglo-Celtic backgrounds are under-represented at familial cancer clinics in the UK, the USA, and Australia. This article discusses cultural beliefs as a potential key barrier to access, reviews previous empirical research on cultural aspects of cancer genetics, draws implications from findings, and sets a research agenda on the inter-relationships between culture, cancer genetics, and kinship., Methods: The CD-ROM databases MEDLINE, PsychLIT, CINAHL, and Sociological Abstracts were searched from 1980 onwards., Results: Cultural aspects of cancer genetics is the focus of an emerging body of publications. Almost all studies assessed African-American women with a family history of breast cancer and few studies included more diverse samples, such as Americans of Ashkenazi Jewish background or Hawaiian- and Japanese-Americans. Our analysis of published reports suggests several directions for future research. First, an increased focus on various Asian societies appears warranted. Research outside North America could explore the extent to which findings can be replicated in other multicultural settings. In addition, control group designs are likely to benefit from systematically assessing culture based beliefs and cultural identity in the "majority culture" group used for comparative purposes., Conclusion: More data on which to base the provision of culturally appropriate familial cancer clinic services to ethnically diverse societies are needed. Empirical data will assist with culturally appropriate categorisation of people from other cultures into risk groups based on their family histories and provide the basis for the development of culturally appropriate patient education strategies and materials.

Human Y-chromosomal short tandem repeat (STR) data provide a potential model system for the understanding of autosomal STR mutations in humans and other species. Yet, the reconstruction of STR evolution is rarely attempted, because of the absence of an appropriate methodology. We here develop and validate a phylogenetic-network approach. We have typed 256 Y chromosomes of indigenous descent from Africa, Asia, Europe, Australia, and highland Papua New Guinea, for the STR loci DYS19, DXYS156Y, DYS389, DYS390, DYS392, and DYS393, as well as for five ancient biallelic mutation events: two poly (A) length variants associated with the YAP insertion, two independent SRY-1532 mutations, and the 92R7 mutation. We have used our previously published pedigree data from 11,000 paternity-tested autosomal STR-allele transfers to produce a two-class weighting system for the Y-STR loci that is based on locus lengths and motif lengths. Reduced-median-network analysis yields a phylogeny that is independently supported by the five biallelic mutations, with an error of 6%. We find the earliest branch in our African San (Bushmen) sample. Assuming an age of 20,000 years for the Native American DYS199 T mutation, we estimate a mutation rate of 2.6x10-4 mutations/20 years for slowly mutating Y STRs, approximately 10-fold slower than the published average pedigree rate.

Research on human origins has tended to focus on the origins of western Eurasians; only recently have genetic studies examined south and east Asian populations in depth. Recent work suggests that the supposed Aryan invasion of India 3,000-4,000 years ago was much less significant than is generally believed.

Micronucleus frequency in epidemiological studies of human exposure has become a preferred biomarker. A generally recognized observation is that micronucleus frequency increases with age. One requirement for comparison of data, which is being generated in many countries, is some common agreement about what constitutes a typical or normal background frequency of micronuclei. This is also a requirement when examining any individual value, especially one which might be considered an outlier. A mean value for normal micronucleus frequency with age is developed via the analysis of multiple studies, all of which employed large population bases and generally were conducted with the intent of determining population values. The result is presented here, with the understanding that it may over- or under-estimate the actual values in certain populations., (Copyright 1999 Elsevier Science B.V.)

Human leukocyte antigen (HLA) class II allogenotyping has been applied to investigate the polymorphism of the DRB, DQB1, DQB2, DQA1, and DQA2 genes in Aborigines from the East Coast of Australia and in Melanesians from the Papua New Guinea North-East Coast and Highlands. Three new DR/DQ arrangements were observed, DRw14/DQB1-2b/DQA1-1a and DRw5Nauru/DQB1-3a/DQA1-2 (n Australian Aborigines), and DRw5Nauru/DQB1-1a/DQA1-1b (in Madang). DQA2 and DQB2 allogenotyping with TaqI and PstI digested genomic DNA revealed little polymorphism among the Papua New Guineans, with DQA2-Xa1 and DQB2-Xb1 the most common alleles in all the groups. However, the presence of DQA2-Xa2 in Papuans and Australian Aborigines reflects the degree of admixture with Caucasoids while the DQA2-Xa4 allele in Madang is probably a marker of Mongoloid origin.