Research of the origin of a particular Tunisian group using a physical marker and Alu insertion polymorphisms

The aim of this study was to show how, in some particular circumstances, a physical marker can be used along with molecular markers in the research of an ancient people movement. A set of five Alu insertions was analysed in 42 subjects from a particular Tunisian group (El Hamma) that has, unlike most of the Tunisian population, a very dark skin, similar to that of sub-Saharans, and in 114 Tunisian subjects (Gabes sample) from the same governorate, but outside the group. Our results showed that the El Hamma group is genetically midway between sub-Saharan populations and North Africans, whereas the Gabes sample is clustered among North Africans. In addition, The A25 Alu insertion, considered characteristic to sub-Saharan Africans, was present in the El Hamma group at a relatively high frequency. This frequency was similar to that found in sub-Saharans from Nigeria, but significantly different from those found in the Gabes sample and in other North African populations. Our molecular results, consistent with the skin color status, suggest a sub-Saharan origin of this particular Tunisian group.     

Craniometric variation of the Ainu: an assessment of differential gene flow from northeast Asia into northern Japan, Hokkaido

In and after the latest Neolithic period in Japan (approximately B.P. 2,300 years), there were two distinct waves of migration from eastern Asia. One is well known as successive episodes in which indigenous inhabitants of main-island Japan were intruded on by new arrivals with advanced technology, and of a different genetic stock. Another migration of people and culture, identified as the Okhotsk culture, reached the northeastern part of Hokkaido. As opposed to main-island Japan, the morphological continuity from the Neolithic to recent inhabitants in Hokkaido (Ainu) is notable, so that the evidence of admixture easily could have escaped notice. In this study, the effects of gene flow from an outside source on the pattern of among-group variation of Hokkaido Ainu are examined by means of two models. One is the R-matrix model comparing observed and expected craniometric variation for estimating differential external gene flow into a region. The other is a simple simulation model that estimates admixture in a population with two parental populations. The two approaches give similar results. The results suggest the possibility of admixture between the migrants from Northeast Asia, the Okhotsk culture people, and the indigenous inhabitants in Hokkaido during the 5th to 12th centuries A.D., at least in northeastern Hokkaido. Such gene flow may have a certain degree of effect on the genetic structure of recent Ainu. The findings further suggest morphological heterogeneity in Northeast Asia during the Holocene that has relevance for understanding the morphological heterogeneity seen through time in the New World.     

Phylogeography of Scots pine in Europe and Asia based on mtDNA polymorphisms

We analyzed mitochondrial DNA polymorphisms to search for evidence of the genetic structure and patterns of admixture in 124 populations (N = 1407 trees) across the distribution of Scots pine in Europe and Asia. The markers revealed only a weak population structure in Central and Eastern Europe and suggested postglacial expansion to middle and northern latitudes from multiple sources. Major mitotype variants include the remnants of Scots pine at the north-western extreme of the distribution in the Scottish Highlands; two main variants (western and central European) that contributed to the contemporary populations in Norway and Sweden; the central-eastern European variant present in the Balkan region, Finland, and Russian Karelia; and a separate one common to most eastern European parts of Russia and western Siberia. We also observe signatures of a distinct refugium located in the northern parts of the Black Sea basin that contributed to the patterns of genetic variation observed in several populations in the Balkans, Ukraine, and western Russia. Some common haplotypes of putative ancient origin were shared among distant populations from Europe and Asia, including the most southern refugial stands that did not participate in postglacial recolonization of northern latitudes. The study indicates different genetic lineages of the species in Europe and provides a set of genetic markers for its finer-scale population history and divergence inference.     

The insertion/deletion polymorphisms in the waxy gene of barley genetic resources from East Asia

The length polymorphism in the waxy gene, which encodes a granule-bound ADP-glucose-glucosyl transferase [granule-bound starch synthase I (GBSS I), E.C. 2.4.1.11] in barley (Hordeum vulgare), was found. The 5′ leader sequence of the waxy gene of barley germplasm from Japan and Korea was analyzed by the polymerase chain reaction (PCR). The waxy gene of these genetic stocks had three types of length polymorphisms, suggesting that there are insertion/deletion mutations at the 5′ leader sequence of the waxy gene. DNA sequence analysis of the polymorphic PCR products showed that: (1) a 403-bp deletion mutation, which included a complete exon I, was found in the wax allele and a 193-bp insertion sequence was located in the intron I, and (2) the insertion sequence was also located in intron I of the Wax allele. The identity of the insertion sequence was completely conserved between the wax allele and the novel Wax allele. These finding s implying that the wax allele, which was found in indigenous waxy barley, originated in non-waxy barley with the novel Wax allele. Received: 12 January 2001 / Accepted: 17 April 2001     

Population analysis of vitamin D receptor polymorphisms and the role of genetic ancestry in an admixed population

The vitamin D receptor (VDR) is an essential protein related to bone metabolism. Some VDR alleles are differentially distributed among ethnic populations and display variable patterns of linkage disequilibrium (LD). In this study, 200 unrelated Brazilians were genotyped using 21 VDR single nucleotide polymorphisms (SNPs) and 28 ancestry informative markers. The patterns of LD and haplotype distribution were compared among Brazilian and the HapMap populations of African (YRI), European (CEU) and Asian (JPT+CHB) origins. Conditional regression and haplotype-specific analysis were performed using estimates of individual genetic ancestry in Brazilians as a quantitative trait. Similar patterns of LD were observed in the 5' and 3' gene regions. However, the frequency distribution of haplotype blocks varied among populations. Conditional regression analysis identified haplotypes associated with European and Amerindian ancestry, but not with the proportion of African ancestry. Individual ancestry estimates were associated with VDR haplotypes. These findings reinforce the need to correct for population stratification when performing genetic association studies in admixed populations.     

Some genetic erythrocyte polymorphisms in the Mbugu and other populations of the Central African Republic with an analysis of genetic distances

Phenotype and gene frequencies of four blood group polymorphisms (ABO, MNSs, Rhesus, and Duffy) as well as hemoglobin types of four populations of the Republic of Central Africa are reported. All these polymorphisms are in Hardy-Weinberg equilibrium. Regarding the four blood group polymorphisms mentioned above the genetic distances according to NEI have been computed for fifteen populations of the Central-Eastern and Central-Western areas of Africa, including the four own samples. The results of these analyses are discussed.     

HIGM syndrome caused by insertion of an AluYb8 element in exon 1 of the <Emphasis Type="Italic">CD40LG</Emphasis> gene

A new mutation of the CD40LG gene that encodes the CD40 ligand molecule was characterized in a young patient harboring a hyper-IgM with immunodeficiency syndrome. Inactivation of CD40LG gene resulted from the insertion of an AluYb8 element in exon 1 responsible for a total deficiency of CD40 ligand expression by T lymphocytes. Maternal transmission of the X-linked mutation was confirmed by gene-specific polymerase chain reaction. This is the 17th case report concerning a human genetic disease caused by an Alu element insertion in a coding sequence.     

Differentiation between subpopulations of a polychromatic damselfly with respect to morph frequencies, but not neutral genetic markers

The damselfly, Nehalennia irene (Hagen), has two distinct female colour morphs. Individuals of one morph have male-like colouration and pattern (androchromes), whereas gynochromes are different from males and androchromes in these respects. In several damselflies, such female-limited polychromatism is attributable to a single genetic locus. We developed six polymorphic genetic markers, which were codominant, to test for genetic differentiation in N. irene, collected from two sites located 8 km from one another in eastern Ontario, Canada. Based on three censuses spanning a 10 year period (1992-2001), morph ratios differed consistently and significantly between these two sites. However, subpopulations at these sites were not genetically differentiated with respect to the putatively neutral markers. Our results suggest that site differences in morph ratios of female N. irene cannot be explained by genetic drift, but are consistent with spatially variable selection operating on different morphs, perhaps mediated by male density. Alternatively, morph type may be a plastic trait and cues for induction may differ between sites.     

Brief communication: Admixture analysis with forensic microsatellites in Minas Gerais,Brazil: The ongoing evolution of the capital and of an African‐derived community

We report the estimated allele frequencies for 13 and 14 microsatellite loci in two populations of Minas Gerais, Brazil as follows: Belo Horizonte (the capital) and Marinhos (an African‐derived community). Analysis of the African, Amerindian, and European genetic contributions to both populations, together with historical information, revealed distinct differences between the two populations. Estimates for Belo Horizonte revealed a higher‐European (66%) than African (32%) contribution, and a minimal Amerindian contribution. These results are consistent with the peopling of the city mainly by people from the Minas Gerais hinterland, a people highly admixed but with more European ancestry. Estimates for Marinhos confirmed the high‐African component of the population. However, a temporal analysis of two datasets—CURRENT (representing the population living in Marinhos today) and ORIGINAL (representing families, who have lived in Marinhos since the onset of the 20th century),—identified a diminishing of the population's African ancestry from 92% in the ORIGINAL group to 67% in the CURRENT group. This change is here interpreted as a consequence of the growing migration into the village of people with more European ancestry and subsequent admixture with the local population. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

Allelic frequencies and statistical data obtained from 12 codis STR loci in an admixed population of the Brazilian Amazon

The allelic frequencies of 12 short tandem repeat loci were obtained from a sample of 307 unrelated individuals living in Macapá, a city in the northern Amazon region, Brazil. These loci are the most commonly used in forensics and paternity testing. Based on the allele frequency obtained for the population of Macapá, we estimated an interethnic admixture for the three parental groups (European, Native American and African) of, respectively, 46%, 35% and 19%. Comparing these allele frequencies with those of other Brazilian populations and of the Iberian Peninsula population, no significant distances were observed. The interpopulation genetic distances (F(ST) coefficients) to the present database ranged from F(ST) = 0.0016 between Macapá and Belém to F(ST) = 0.0036 between Macapá and the Iberian Peninsula.     

Reconstructing the Human Genetic History of Mainland Southeast Asia: Insights from Genome-Wide Data from Thailand and Laos

Thailand and Laos, located in the center of Mainland Southeast Asia (MSEA), harbor diverse ethnolinguistic groups encompassing all five language families of MSEA: Tai-Kadai (TK), Austroasiatic (AA), Sino-Tibetan (ST), Hmong-Mien (HM), and Austronesian (AN). Previous genetic studies of Thai/Lao populations have focused almost exclusively on uniparental markers and there is a paucity of genome-wide studies. We therefore generated genome-wide SNP data for 33 ethnolinguistic groups, belonging to the five MSEA language families from Thailand and Laos, and analyzed these together with data from modern Asian populations and SEA ancient samples. Overall, we find genetic structure according to language family, albeit with heterogeneity in the AA-, HM-, and ST-speaking groups, and in the hill tribes, that reflects both population interactions and genetic drift. For the TK speaking groups, we find localized genetic structure that is driven by different levels of interaction with other groups in the same geographic region. Several Thai groups exhibit admixture from South Asia, which we date to ∼600–1000 years ago, corresponding to a time of intensive international trade networks that had a major cultural impact on Thailand. An AN group from Southern Thailand shows both South Asian admixture as well as overall affinities with AA-speaking groups in the region, suggesting an impact of cultural diffusion. Overall, we provide the first detailed insights into the genetic profiles of Thai/Lao ethnolinguistic groups, which should be helpful for reconstructing human genetic history in MSEA and selecting populations for participation in ongoing whole genome sequence and biomedical studies.     

Failure to support a genetic contribution of AKT1 polymorphisms and altered AKT signaling in schizophrenia

The protein kinase v-akt murine thymoma viral oncogene homolog (AKT) gene family comprises three human homologs that phosphorylate and inactivate glycogen synthase kinase 3beta (GSK3beta). Studies have reported the genetic association of AKT1 with schizophrenia. Additionally, decreased AKT1 protein expression and the reduced phosphorylation of GSK3beta were reported in this disease, leading to a new theory of attenuated AKT1-GSK3beta signaling in schizophrenia pathogenesis. We have evaluated this theory by performing both genetic and protein expression analyses. A family based association test of AKT1 did not show association with schizophrenia in Japanese subjects. The expression levels of total AKT, AKT1 and phosphorylated GSK3beta detected in the schizophrenic brains from two different brain banks also failed to support the theory. In addition, no attenuated AKT-GSK3beta signaling was observed in the lymphocytes from Japanese schizophrenics, contrasting with previous findings. Importantly, we found that the level of phosphorylated GSK3beta at Ser9 tended to be inversely correlated with postmortem intervals, and that the phosphorylation levels of AKT were inversely correlated with brain pH, issues not assessed in the previous study. These data introduce a note of caution when estimating the phosphorylation levels of GSK3beta and AKT in postmortem brains. Collectively, this study failed to support reduced signaling of the AKT-GSK3beta molecular cascade in schizophrenia.     

Optimality of the genetic code with respect to protein stability and amino-acid frequencies

Background

The genetic code is known to be efficient in limiting the effect of mistranslation errors. A misread codon often codes for the same amino acid or one with similar biochemical properties, so the structure and function of the coded protein remain relatively unaltered. Previous studies have attempted to address this question quantitatively, by estimating the fraction of randomly generated codes that do better than the genetic code in respect of overall robustness. We extended these results by investigating the role of amino-acid frequencies in the optimality of the genetic code.

Results

We found that taking the amino-acid frequency into account decreases the fraction of random codes that beat the natural code. This effect is particularly pronounced when more refined measures of the amino-acid substitution cost are used than hydrophobicity. To show this, we devised a new cost function by evaluating in silico the change in folding free energy caused by all possible point mutations in a set of protein structures. With this function, which measures protein stability while being unrelated to the code's structure, we estimated that around two random codes in a billion (10⁹) are fitter than the natural code. When alternative codes are restricted to those that interchange biosynthetically related amino acids, the genetic code appears even more optimal.

Conclusions

These results lead us to discuss the role of amino-acid frequencies and other parameters in the genetic code's evolution, in an attempt to propose a tentative picture of primitive life.     

Sixty years of anthropogenic pressure: a spatio-temporal genetic analysis of brown trout populations subject to stocking and population declines

Analyses of historical samples can provide invaluable information on changes to the genetic composition of natural populations resulting from human activities. Here, we analyse 21 microsatellite loci in historical (archived scales from 1927 to 1956) and contemporary samples of brown trout ( Salmo trutta ) from six neighbouring rivers in Denmark, to compare the genetic structure of wild populations before and after population declines and stocking with nonlocal strains of hatchery trout. We show that all populations have been strongly affected by stocking, with admixture proportions ranging from 14 to 64%. Historical population genetic structure was characterized by isolation by distance and by positive correlations between historical effective population sizes and habitat area within river systems. Contemporary population genetic structure still showed isolation by distance, but also reflected differences among populations in hatchery trout admixture proportions. Despite significant changes to the genetic composition within populations over time, dispersal rates among populations were roughly similar before and after stocking. We also assessed whether population declines or introgression by hatchery strain trout should be the most significant conservation concern in this system. Based on theoretical considerations, we argue that population declines have had limited negative effects for the persistence of adaptive variation, but admixture with hatchery trout may have resulted in reduced local adaptation. Collectively, our study demonstrates the usefulness of analysing historical samples for identifying the most important consequences of human activities on the genetic structure of wild populations.     

Extensive ethnolinguistic diversity at the crossroads of North China and South Siberia reflects multiple sources of genetic diversity

North China and South Siberia, populated by Altaic- and Sino-Tibetan-speaking populations, possess extensive ethnolinguistic diversity and serve as the crossroads for the initial peopling of America and western–eastern transcontinental communication. However, the population genetic structure and admixture history of northern East Asians remain poorly understood due to a lack of genome-wide data, especially for Mongolic-speaking people in China. We genotyped genome-wide single nucleotide polymorphisms for 510 individuals from 38 Mongolic, Tungusic, and Sinitic-speaking populations. We first explored the shared alleles and haplotypes within the studied groups. We then merged with 3508 published modern and ancient Eurasian individuals to reconstruct the deep evolutionary and natural selection history of northern East Asians. We identified genetic substructures within Altaic-speaking populations: Western Turkic people harbored more western Eurasian-related ancestry; Northern Mongolic people in Siberia and eastern Tungusic people in Amur River Basin (ARB) possessed a majority of Neolithic ARB related ancestry; Southern Mongolic people in China possessed apparent genetic influence from Neolithic Yellow River Basin (YRB) farmers. Additionally, we found the differentiated admixture history between western and eastern Mongolians and geographically close Northeast Hans: the former received a genetic impact from western Eurasians, and the latter retained the primary Neolithic YRB and ARB ancestry. Moreover, we demonstrated that Kalmyk people from the northern Caucasus Mountains possessed a strong genetic affinity with Neolithic Mongolian Plateau (MP) people, supporting the hypothesis of their eastern Eurasian origin and long-distance migration history. We also illuminated that historical pastoral empires in the MP contributed considerably to the gene pool of northern Mongolic people but rarely to the southern ones. We finally found natural selection signatures in Mongolians associated with alcohol metabolism. Our results demonstrated that the Neolithic ancestral sources from the MP or ARB played an important role in spreading Altaic populations and languages. The observed multisources of genetic diversity contributed significantly to the extensive ethnolinguistic diversity in northern East Asia.     

Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population

Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160C<A) genes has been reported on Bangladeshi population relating those with colorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR = 2.58, 95% CI = 1.77–3.77, p < 0.05) and Pro/Pro mutant homozygosity (adjusted OR = 2.92, 95% CI = 1.78–4.78, p < 0.05) along with the combined genotype (Arg/Pro + Pro/Pro) (adjusted OR = 2.70, 95% CI = 1.90–3.82, p < 0.05) and colorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (p < 0.05) found to be associated with colorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR = 2.02, 95% CI = 1.42–2.87, p < 0.05). In conclusion, heterozygosity and mutant homozygosity as well as the combination of both TP53 Arg72Pro and CDH1 rs16260 polymorphisms are responsible to increase the risk of colorectal cancer development in Bangladeshi population.     

Impacts of acidification on brown trout Salmo trutta populations and the contribution of stocking to population recovery and genetic diversity

Anthropogenic acidification in SW-Scotland, from the early 19th Century onwards, led to the extinction of several loch (lake) brown trout (Salmo trutta) populations and substantial reductions in numbers in many others. Higher altitude populations with no stocking influence, which are isolated above natural and artificial barriers and subjected to the greatest effect of acidification, exhibited the least intrapopulation genetic diversity (34% of the allelic richness of the populations accessible to anadromous S. trutta). These, however, were characterised by the greatest interpopulation divergence (highest pairwise D_EST 0.61 and F_ST 0.53 in contemporary samples) based on 16 microsatellite loci and are among the most differentiated S. trutta populations in NW-Europe. Five lochs above impassable waterfalls, where S. trutta were thought to be extinct, are documented as having been stocked in the late 1980s or 1990s. All five lochs now support self-sustaining S. trutta populations; three as a direct result of restoration stocking and two adjoining lochs largely arising from a small remnant wild population in one, but with some stocking input. The genetically unique Loch Grannoch S. trutta, which has been shown to have a heritable increased tolerance to acid conditions, was successfully used as a donor stock to restore populations in two acidic lochs. Loch Fleet S. trutta, which were re-established from four separate donor sources in the late 1980s, showed differential contribution from these ancestors and a higher genetic diversity than all 17 natural loch populations examined in the area. Genetically distinct inlet and outlet spawning S. trutta populations were found in this loch. Three genetically distinct sympatric populations of S. trutta were identified in Loch Grannoch, most likely representing recruitment from the three main spawning rivers. A distinct genetic signature of Loch Leven S. trutta, the progenitor of many Scottish farm strains, facilitated detection of stocking with these strains. One artificially created loch was shown to have a population genetically very similar to Loch Leven S. trutta. In spite of recorded historical supplemental stocking with Loch Leven derived farm strains, much of the indigenous S. trutta genetic diversity in the area remains intact, aside from the effects of acidification induced bottlenecks. Overall genetic diversity and extant populations have been increased by allochthonous stocking.