A shortcut to the gene pool. Big pharmaceutical companies join forces to map out genetic signposts.
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The genetic structure of five cattle breeds from Ukraine was investigated using ISSR-PCR method. Breeding- and sex-specific spectra of amplification products were revealed with two threenucleotide microsatellite primers. The possibility of using ISSR-PCR markers for characterization of genetic relations between breeds of cattle were evaluated.
Several lines of evidence over the last decade have established that G protein-coupled receptors (GPCRs) can signal in the absence of their natural ligand which results in ligand-independent or constitutive activity. Natural genetic mutation, overexpression and site-directed mutagenesis all result in constitutive activation of GPCRs. Of the 100 leading pharmaceutical products in 2000, 39, wholly or in part, acted through a GPCR-mediated mechanism, a fact that underlines the extreme importance of GPCRs as pharmaceutical drug targets. In addition, the sequencing of the human genome and database mining has revealed that there are hundreds of putative orphan GPCRs for which the natural ligands have not been identified. These orphan GPCRs have largely been inaccessible to drug discovery because traditional methods have mainly relied on ligand-dependent binding assays to discover and pharmacologically characterize potential drug candidates from this receptor class. In the absence of ligand identification, constitutively active receptors allow for a logical and direct way forward through the drug discovery pathway by providing the tool necessary to find modulators of this receptor class in a ligand-independent fashion.
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Phylogenetic and diversity analysis of the mtDNA control region sequence variation of 821 individuals from Europe and the Middle East distinguishes five major lineage groups with different internal diversities and divergence times. Consideration of the diversities and geographic distribution of these groups within Europe and the Middle East leads to the conclusion that ancestors of the great majority of modern, extant lineages entered Europe during the Upper Paleolithic. A further set of lineages arrived from the Middle East much later, and their age and geographic distribution within Europe correlates well with archaeological evidence for two culturally and geographically distinct Neolithic colonization events that are associated with the spread of agriculture. It follows from this interpretation that the major extant lineages throughout Europe predate the Neolithic expansion and that the spread of agriculture was a substantially indigenous development accompanied by only a relatively minor component of contemporary Middle Eastern agriculturalists. There is no evidence of any surviving Neanderthal lineages among modern Europeans.
Fulani of Burkina Faso (West Africa) are a particularly interesting ethnic group because of their lower susceptibility to Plasmodium falciparum malaria as compared to sympatric populations, Mossi and Rimaibé. Moreover, the occurrence of a Caucasoid component in their genetic make-up has been suggested on the basis of their physical traits and cultural traditions even though this view was not supported by genetic studies. A total of 149 unrelated subjects (53 Mossi, 47 Rimaibé and 49 Fulani) have been typed for 97 HLA class I alleles with the amplification refractory mutation system/polymerase chain reaction (ARMS/PCR) technique. Mossi and Rimaibé data were pooled since none of the 42 statistically testable alleles exhibited a significant heterogeneity. These pooled gene frequencies were found to be very different from those of Fulani: a certain (P<0.001) or a likely (0.001 <P<0.01) difference was found for 5 and 12 alleles, respectively. Four alleles (A*24, A*29, B*27, B*3701) appeared to be essentially "private" Fulani alleles with respect to the other two populations but their presence was not associated with higher resistance to P. falciparum. Our data have then been compared using chord distances (CD) with those from the literature on Africans (including Gambian Fulani) and Caucasoids. The Burkina Faso and Gambian Fulani turned out to be very different (CD=2.191). Moreover, Burkina Faso Fulani were very distant from sympatric Mossi and Rimaibé (CDs=1.912 and 1.884), whereas Gambian Fulani were similar to sympatric Mandinka and Wolof (CDs=0.412 and 0.388) to an extent comparable to that found between Mossi and Rimaibé (CD=0.555). Our study does not suggest the involvement of HLA I in the higher resistance to malaria of Fulani, and confirms a low, if any, Caucasoid component in their gene pool.
OBJECTIVE: To study the genetic polymorphism of Y chromosome in different Chinese ethnic group populations. METHODS: Genotypes of 17 biallelic markers located in the nonrecombining portion of the Y chromosome in 76 men from 3 Chinese ethnic group populations (Han in Shandong, Bai in Yunnan, and Tu in Qinghai) were examined with polymerase chain reaction (PCR) and allelic-specific PCR (ASPCR). Their haplotypes made of these 17 binary markers were constructed. The principle component (PC) analysis was conducted based on the haplotype frequency distribution among these 3 and other 15 published Chinese ethnic group populations. RESULTS: The diversities of M50, M110, M103, M88, M3, and M7 were not found in these 3 populations. The frequencies of YAP+ were 23.8%, 6.7%, and 4% respectively in Tu, Bai, and Shandong Han. Eleven haplotypes were found in 3 populations--7 haplotypes (H1, H3, H5, H6, H8, H9, and H11) in Shandong Han (Han.SD), 8 haplotypes (H1, H2, H3, H5, H6, H8, H11, and H16) in Tu, and 9 haplotypes (H1, H3, H4, H5, H6, H8, H9, H11, and H13) in Bai. The predominant haplotypes were H1, H3, H5, H6, H8, and H11. According to PC analysis, Bai was close to Northern Han; Shandong Han, Southern Han (Han.S), Bai and Yunnan Tibetan clustered together; and Tu was close to Yi, Hui and Manchurian. CONCLUSIONS: Shandong Han may have had genetic exchanges with southern populations in China. It has been confirmed that some gene components of Han had flowed into Bai's gene pool. Gene flowed from Central Asia had impacted Chinese western populations.
A diversity survey was used to estimate allelic diversity and heterozygosity of 129 microsatellite markers in a panel of 44 common bean (Phaseolus vulgaris L.) genotypes that have been used as parents of mapping populations. Two types of microsatellites were evaluated, based respectively on gene coding and genomic sequences. Genetic diversity was evaluated by estimating the polymorphism information content (PIC), as well as the distribution and range of alleles sizes. Gene-based microsatellites proved to be less polymorphic than genomic microsatellites in terms of both number of alleles (6.0 vs. 9.2) and PIC values (0.446 vs. 0.594) while greater size differences between the largest and the smallest allele were observed for the genomic microsatellites than for the gene-based microsatellites (31.4 vs. 19.1 bp). Markers that showed a high number of alleles were identified with a maximum of 28 alleles for the marker BMd1. The microsatellites were useful for distinguishing Andean and Mesoamerican genotypes, for uncovering the races within each genepool and for separating wild accessions from cultivars. Greater polymorphism and race structure was found within the Andean gene pool than within the Mesoamerican gene pool and polymorphism rate between genotypes was consistent with genepool and race identity. Comparisons between Andean genotypes had higher polymorphism (53.0%) on average than comparisons among Mesoamerican genotypes (33.4%). Within the Mesoamerican parental combinations, the intra-racial combinations between Mesoamerica and Durango or Jalisco race genotypes showed higher average rates of polymorphism (37.5%) than the within-race combinations between Mesoamerica race genotypes (31.7%). In multiple correspondance analysis we found two principal clusters of genotypes corresponding to the Mesoamerican and Andean gene pools and subgroups representing specific races especially for the Nueva Granada and Peru races of the Andean gene pool. Intra population diversity was higher within the Andean genepool than within the Mesoamerican genepool and this pattern was observed for both gene-based and genomic microsatellites. Furthermore, intra-population diversity within the Andean races (0.356 on average) was higher than within the Mesoamerican races (0.302). Within the Andean gene pool, race Peru had higher diversity compared to race Nueva Granada, while within the Mesoamerican gene pool, the races Durango, Guatemala and Jalisco had comparable levels of diversity which were below that of race Mesoamerica.
Genetic diversity within a common bean ( Phaseolus vulgaris L.) collection, comprising 343 accessions from the Iberian Peninsula, was examined using six allozyme markers. Two major clusters corresponding to the Andean and Mesoamerican gene pools were identified. Both gene pools were characterized by specific alleles, with the former exhibiting Skdh(100), Me(100), Rbcs(100 or 98) and Diap-1(100), and the latter exhibiting Skdh(103), Me(100), Rbcs(100) and Diap-1(95). Some accessions from both clusters, deviating from these allozyme patterns, exhibited Skdh(100), Me(100), Rbcs(100) and Diap-1(95) or Skdh(103), Me(100), Rbcs(100) and Diap-1(100) allozyme profiles and were considered as putative hybrids.The levels of genetic variation has not been eroded since the introduction of the common bean from the American centers of domestication to the Iberian Peninsula. Instead, obvious signs of introgression between the two gene pools were observed, mainly among white-seeded genotypes. The intermediate forms adapted to the Iberian Peninsula could have emerged from initial recombination between Mesoamerican and Andean gene pools. The Iberian common bean germplasm is therefore more complex than previously thought, and contains additional diversity that remains to be explored for genetic and breeding purposes. The Iberian Peninsula could be considered as a secondary center of genetic diversity of the common bean, especially the large white-seeded genotypes.
Nucleotide sequences of the mitochondrial DNA (mtDNA) control region were studied in Germans living in the Altai, Russia. Although this ethnic group has been living in Russia for a long time, the obtained data indicate that its mitochondrial gene pool retains the main characteristics of the Western and Central European gene pools. Regarding the mitochondrial gene pool, Russian Germans were more similar to Germans living in Germany than to Russians with regard to the frequency of the Cambridge nucleotide sequence, frequencies and composition of five European haplotypic groups (classification of Richards et al.), and average intra- and interpopulation pairwise nucleotide differences. However, the mitochondrial gene pool of Altaian Germans also differed from that of Western European populations. The gene pool of Altaian Germans contained the ancestral variants of the main haplotypic groups. To date, these variants have not been found in modern Western and Central European populations, which is apparently due to their lower frequencies. In addition, some previously unknown mtDNA variants with specific nucleotide substitutions were found in Altaian Germans. The obtained results suggest that the modern mitochondrial gene pool of Europeans, including Germans from Germany, was largely affected by the demographic processes that occurred in the past two centuries. The Germans that lived in Russia were relatively isolated and, hence, retained more characteristics of the ancestral gene pool.
The distribution of identical and similar (phylogenetically related) types of hypervariable segment 1 (HVS1) of the mitochondrial DNA (mtDNA) was studied in human populations belonging to three Slavonic groups and nine ethnogeographic groups of Eurasia (total sample size 2772 people). The results testified to a common origin of West, South, and East Slavs and revealed a central place of West Slavs among all Slavonic ethnoses. Mixing was shown to play a substantial role in the formation of specific features of all three Slavonic gene pools. The mitochondrial gene pools of the Slavonic ethnoses proved to preserve features suggesting a common ancestor for these and South European populations (especially those of the Balkan Peninsula).