The molecular genetics of European ancestry.
(9/6490)
In an earlier paper we proposed, on the basis of mitochondrial control region variation, that the bulk of modern European mitochondrial DNA(mtDNA) diversity had its roots in the European Upper Palaeolithic. Refining the mtDNA phylogeny and enlarging the sample size both within Europe and the Middle East still support this interpretation and indicate three separate phases of colonization: (i) the Early Upper Palaeolithic about 50,000 BP; (ii) the Late Upper Palaeolithic 11,000-14,000 BP; and (iii) the Neolithic from 8500 BP. (+info)
Molecular genetic evidence for the human settlement of the Pacific: analysis of mitochondrial DNA, Y chromosome and HLA markers.
(10/6490)
Present-day Pacific islanders are thought to be the descendants of Neolithic agriculturalists who expanded from island South-east Asia several thousand years ago. They speak languages belonging to the Austronesian language family, spoken today in an area spanning half of the circumference of the world, from Madagascar to Easter Island, and from Taiwan to New Zealand. To investigate the genetic affinities of the Austronesian-speaking peoples, we analysed mitochondrial DNA, HLA and Y-chromosome polymorphisms in individuals from eight geographical locations in Asia and the Pacific (China, Taiwan, Java, New Guinea highlands, New Guinea coast, Trobriand Islands, New Britain and Western Samoa). Our results show that the demographic expansion of the Austronesians has left a genetic footprint. However, there is no simple correlation between languages and genes in the Pacific. (+info)
Analysis of ancient DNA from a prehistoric Amerindian cemetery.
(11/6490)
The Norris Farms No. 36 cemetery in central Illinois has been the subject of considerable archaeological and genetic research. Both mitochondrial DNA (mtDNA) and nuclear DNA have been examined in this 700-year-old population. DNA preservation at the site was good, with about 70% of the samples producing mtDNA results and approximately 15% yielding nuclear DNA data. All four of the major Amerindian mtDNA haplogroups were found, in addition to a fifth haplogroup. Sequences of the first hypervariable region of the mtDNA control region revealed a high level of diversity in the Norris Farms population and confirmed that the fifth haplogroup associates with Mongolian sequences and hence is probably authentic. Other than a possible reduction in the number of rare mtDNA lineages in many populations, it does not appear as if European contact significantly altered patterns of Amerindian mtDNA variation, despite the large decrease in population size that occurred. For nuclear DNA analysis, a novel method for DNA-based sex identification that uses nucleotide differences between the X and Y copies of the amelogenin gene was developed and applied successfully in approximately 20 individuals. Despite the well-known problems of poor DNA preservation and the ever-present possibility of contamination with modern DNA, genetic analysis of the Norris Farms No. 36 population demonstrates that ancient DNA can be a fruitful source of new insights into prehistoric populations. (+info)
Sex-biased dispersal in sperm whales: contrasting mitochondrial and nuclear genetic structure of global populations.
(12/6490)
The social organization of most mammals is characterized by female philopatry and male dispersal. Such sex-biased dispersal can cause the genetic structure of populations to differ between the maternally inherited mitochondrial DNA (mtDNA) and the bi-parental nuclear genome. Here we report on the global genetic structure of oceanic populations of the sperm whale, one of the most widely distributed mammalian species. Groups of females and juveniles are mainly found at low latitudes, while males reach polar waters, returning to tropical and subtropical waters to breed. In comparisons between oceans, we did not find significant heterogeneity in allele frequencies of microsatellite loci (exact test; p = 0.23). Estimates of GST = 0.001 and RST = 0.005 also indicated negligible if any nuclear DNA differentiation. We have previously reported significant differentiation between oceans in mtDNA sequences. These contrasting patterns suggest that interoceanic movements have been more prevalent among males than among females, consistent with observations of females being the philopatric sex and having a more limited latitudinal distribution than males. Consequently, the typical mammalian dispersal pattern may have operated on a global scale in sperm whales. (+info)
Lineage selection and the evolution of multistage carcinogenesis.
(13/6490)
A wide array of proto-oncogenes and tumour suppressor genes are involved in the prevention of cancer. Each form of cancer requires mutations in a characteristic group of genes, but no single group controls all cancers. This lack of generality shows that the control of cancer is not an ancient, fixed property of cells. By contrast, it supports a dynamic evolutionary model, whereby genetic controls over unregulated cell growth are recruited independently through evolutionary time in different tissues within different taxa. The complexity of this genetic control can be predicted from a population genetic model of lineage selection driven by the detrimental fitness effects of cancer. Cancer occurs because the genetic control of cell growth is vulnerable to somatic mutations (or 'hits'), particularly in large, continuously dividing tissues. Thus, compared to small rodents, humans must have evolved more complex genetic controls over cell growth in at least some of their tissues because of their greater size and longevity; an expectation relevant to the application of mouse data to humans. Similarly, the 'two-hit' model so successfully applied to retinoblastoma, which originates in a small embryonic tissue, is unlikely to be generally applicable to other human cancers; instead, more complex scenarios are expected to dominate, with complexity depending upon a tissue's size and its pattern of proliferation. (+info)
Analysis of myocilin mutations in 1703 glaucoma patients from five different populations.
(14/6490)
A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations. (+info)
Mitochondrial sequence variation suggests an African influence in Portuguese cattle.
(15/6490)
A total of 49 samples from indigenous Portuguese cattle breeds were analysed for sequence variation in the hypervariable region of the mitochondrial DNA D-loop. Sequence comparison and phylogenetic analyses revealed that haplotypes fell into two distinct groups. These corresponded with two separate haplotype clusters into which, respectively, all African, or alternatively all sequences of European origin, have previously been shown to fall. Here, the majority of sequences of African type were encountered in three southern, as compared to three northern breeds. This pattern of African influence may reflect an intercontinental admixture in the initial origins of Iberian breeds, or it is perhaps an introgression dating from the long and influential Moorish occupation of the south of the Iberian peninsula. (+info)
Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study.
(16/6490)
Breast cancers arising in women with and without a germline mutation in the BRCA1 or BRCA2 gene display different histological features, which suggests unique mechanisms of molecular pathogenesis: We used a molecular pathological analysis to define the genetic abnormalities relevant to these specific pathogeneses. Tumor material was studied from 40 women with breast cancer diagnosed before 40 years of age, sampled from a population-based study and stratified by BRCA1 and BRCA2 germline mutation status. Cases were not selected for family history or ethnic origin, and none were known to be genetically related. Thus, germline mutation itself is likely to impact on the molecular pathogenesis of these tumors, with no substantial influence due to modifying genetic or environmental factors. Breast cancers occurring in BRCA1 mutation carriers had significantly higher levels of p53 expression, including the preinvasive (carcinoma in situ) stage of disease, compared with cancers occurring in BRCA2 mutation carriers or women with no detectable germline mutation. These cancers also had a higher proliferation rate as measured by Ki-67 antibody. Expression of the prognostic factors c-erbB-2, cyclin D1, and estrogen receptor was significantly less common in BRCA1 mutation carriers. Lower levels of cyclin D1 were also found in cancers from BRCA2 mutation carriers compared with non-mutation carriers. Direct p53 mutation analysis revealed mutations in 18% of all of the early-onset breast cancers within the study and included rare insertion and deletional mutations in cancers from BRCA1 mutation carriers. Our data indicate that a BRCA1 breast cancer phenotype may be recognized by an exceptionally high proliferation rate and early and frequent p53 overexpression but infrequent selection for overexpression of several other prognostic factor proteins known to be involved in breast oncogenesis. In contrast, breast cancers arising in BRCA2 mutation carriers have a more heterogeneous phenotypic profile. (+info)