Admixture and genetic relationships of Mexican Mestizos regarding Latin American and Caribbean populations based on 13 CODIS-STRs.

Short tandem repeats (STRs) of the combined DNA index system (CODIS) are probably the most employed markers for human identification purposes. STR databases generated to interpret DNA profiles are also helpful for anthropological purposes. In this work, we report admixture, population structure, and genetic relationships of Mexican Mestizos with respect to Latin American and Caribbean populations based on 13 CODIS-STRs. In addition, new STR population data were included from Tijuana, Baja California (Northwest, Mexico), which represents an interesting case of elevated genetic flow as a bordering city with the USA. Inter-population analyses included CODIS-STR data from 11 Mexican Mestizo, 12 Latin American and four Caribbean populations, in addition to European, Amerindian, and African genetic pools as ancestral references. We report allele frequencies and statistical parameters of forensic interest (PD, PE, Het, PIC, typical PI), for 15 STRs in Tijuana, Baja California. This Mexican border city was peculiar by the increase of African ancestry, and by presenting three STRs in Hardy-Weinberg disequilibrium, probably explained by recurrent gene flow. The Amerindian ancestry in Central and Southeast of Mexico was the greatest in Latin America (50.9-68.6%), only comparable with the North of Central America and Ecuador (48.8-56.4%), whereas the European ancestry was prevalent in South America (66.7-75%). The African ancestry in Mexico was the smallest (2.2-6.3%) in Latin America (≥ 2.6%), particularly regarding Brazil (21%), Honduras (62%), and the Caribbean (43.2-65.2%). CODIS-STRs allowed detecting significant population structure in Latin America based on greater presence of European, Amerindian, and African ancestries in Central/South America, Mexican Mestizos, and the Caribbean, respectively.

Differential immunoglobulin class-mediated responses to components of the U1 small nuclear ribonucleoprotein particle in systemic lupus erythematosus and mixed connective tissue disease.

OBJECTIVE: The objective of this paper is to determine whether patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) possess differential IgM- and IgG-specific reactivity against peptides from the U1 small nuclear ribonucleoprotein particle (U1 snRNP). METHODS: The IgM- and IgG-mediated responses against 15 peptides from subunits of the U1 snRNP were assessed by indirect enzyme linked immunosorbent assays (ELISAs) in sera from patients with SLE and MCTD and healthy individuals (n = 81, 41, and 31, respectively). Additionally, 42 laboratory tests and 40 clinical symptoms were evaluated to uncover potential differences. Binomial logistic regression analyses (BLR) were performed to construct models to support the independent nature of SLE and MCTD. Receiver operating characteristic (ROC) curves corroborated the classification power of the models. RESULTS: We analyzed IgM and IgG anti-U1 snRNP titers to classify SLE and MCTD patients. IgG anti-U1 snRNP reactivity segregates SLE and MCTD from nondisease controls with an accuracy of 94.1% while IgM-specific anti-U1 snRNP responses distinguish SLE from MCTD patients with an accuracy of 71.3%. Comparison of the IgG and IgM anti-U1 snRNP approach with clinical tests used for diagnosing SLE and MCTD revealed that our method is the best classification tool of those analyzed (p ≤ 0.0001). CONCLUSIONS: Our IgM anti-U1 snRNP system along with lab tests and symptoms provide additional molecular and clinical evidence to support the hypothesis that SLE and MCTD may be distinct syndromes.

Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease.

Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are autoimmune illnesses characterized by the presence of high titers of autoantibodies directed against a wide range of 'self ' antigens. Proteins of the U1 small nuclear ribonucleoprotein particle (U1 snRNP) are among the most immunogenic molecules in patients with SLE and MCTD. The recent release of a crystallized U1 snRNP provides a unique opportunity to evaluate the effects of tertiary and quaternary structures on autoantigenicity within the U1 snRNP. In the present study, an epitope map was created using the U1 snRNP crystal structure. A total of 15 peptides were tested in a cohort of 68 patients with SLE, 29 with MCTD and 26 healthy individuals and mapped onto the U1 snRNP structure. Antigenic sites were detected in a variety of structures and appear to include RNA binding domains, but mostly exclude regions necessary for protein-protein interactions. These data suggest that while some autoantibodies may target U1 snRNP proteins as monomers or apoptosis-induced, protease-digested fragments, others may recognize epitopes on assembled protein subcomplexes of the U1 snRNP. Although nearly all of the peptides are strong predictors of autoimmune illness, none were successful at distinguishing between SLE and MCTD. The antigenicity of some peptides significantly correlated with several clinical symptoms. This investigation implicitly highlights the complexities of autoimmune epitopes, and autoimmune illnesses in general, and demonstrates the variability of antigens in patient populations, all of which contribute to difficult clinical diagnoses.

The genetic legacy of the Transatlantic Slave Trade in the island of New Providence.

The Bahamian archipelago has been influenced by a wide array of settlers (Lucayans, Eleutherian Adventurers, British Loyalists, Creoles from the United States and African slaves) throughout its short but dynamic history. Nevertheless, the Bahamas remains poorly characterized genetically and little is known about each group's contribution to the island chain. In the current study, the population of New Providence was analyzed based on 15 autosomal STR loci routinely employed in forensic DNA fingerprinting applications. A comparison of this collection with African groups reveals similar genetic profiles to West African populations from Equatorial Guinea and Angola, possibly resulting from the importation of slaves from West African ports during the Transatlantic Slave Trade. Although the New Providence collection exhibits strong genetic affinities to the two US African American reference populations, the detection of unique alleles among them may necessitate the utilization of population-specific databases in forensic cases especially when the STR profiles include these specific variants.

Mitochondrial DNA haplogroup diversity in Basques: a reassessment based on HVI and HVII polymorphisms.

This study provides a more complete characterization of the mitochondrial genome variability of the Basques, including data on the hypervariable segment HVII of the D-loop region, which remains relatively unknown. To that end, genomic DNA from 55 healthy men living in the Arratia Valley (Biscay province) and the Goiherri region (Guipúzcoa province) was examined by direct sequencing. Three-generation pedigree charts were compiled to ensure the collection from autochthonous individuals. The most notable findings emerging from the analysis of haplogroup composition are: (i) lack of U8a mitochondrial lineage, a rare subhaplogroup recently identified in Basques and proposed as a Paleolithic marker, (ii) low frequency of haplogroup V, which conflicts with results of earlier analyses describing high frequencies in southwestern Europe, and (iii) high frequency of haplogroup J, especially subhaplogroups J1c1 and J2a. The frequency of haplogroup J does not coincide with previous mtDNA studies in present-day Basques, but is congruent with frequencies found in prehistoric and historic Basque populations. In explaining divergence in haplogroup composition between modern Basque samples, we hypothesized spatial heterogeneity promoted by population fragmentation due to extreme limitation of dispersal opportunities during the Pleistocene glaciations. Similarities between extinct and extant Basque populations as for the high frequency of lineage J, as well as the abundance of this haplogroup in northern Spain endorse a shift in the focus of attention of mtDNA analysts. A refined dissection of haplogroup J might provide more solid evidence about the process of postglacial recolonization of Europe, and thus about the shaping of the European gene pool.

Structure-based classification of 45 FK506-binding proteins.

The FK506-binding proteins (FKBPs) are a unique group of chaperones found in a wide variety of organisms. They perform a number of cellular functions including protein folding, regulation of cytokines, transport of steroid receptor complexes, nucleic acid binding, histone assembly, and modulation of apoptosis. These functions are mediated by specific domains that adopt distinct tertiary conformations. Using the Threading/ASSEmbly/Refinement (TASSER) approach, tertiary structures were predicted for a total of 45 FKBPs in 23 species. These models were compared with previously characterized FKBP solution structures and the predicted structures were employed to identify groups of homologous proteins. The resulting classification may be utilized to infer functional roles of newly discovered FKBPs. The three-dimensional conformations revealed that this family may have undergone several modifications throughout evolution, including loss of N- and C-terminal regions, duplication of FKBP domains as well as insertions of entire functional motifs. Docking simulations suggest that additional sequence segments outside FKBP domains may modulate the binding affinity of FKBPs to immunosuppressive drugs. The docking models also indicate the presence of a helix-loop-helix (HLH) region within a subset of FKBPs, which may be responsible for the interaction between this group of proteins and nucleic acids.

Austronesian genetic signature in East African Madagascar and Polynesia.

The dispersal of the Austronesian language family from Southeast Asia represents the last major diaspora leading to the peopling of Oceania to the East and the Indian Ocean to the West. Several theories have been proposed to explain the current locations, and the linguistic and cultural diversity of Austronesian populations. However, the existing data do not support unequivocally any given migrational scenario. In the current study, the genetic profile of 15 autosomal STR loci is reported for the first time for two populations from opposite poles of the Austronesian range, Madagascar at the West and Tonga to the East. These collections are also compared to geographically targeted reference populations of Austronesian descent in order to investigate their current relationships and potential source population(s) within Southeast Asia. Our results indicate that while Madagascar derives 66.3% of its genetic makeup from Africa, a clear connection between the East African island and Southeast Asia can be discerned. The data suggest that although geographic location has influenced the phylogenetic relationships between Austronesian populations, a genetic connection that binds them beyond geographical divides is apparent.

Autosomal microsatellite variability of the Arrernte people of Australia.

The genomic diversity of the Arrernte people of Australia or caterpillar people was investigated utilizing 13 autosomal short tandem repeat (STR) markers. Significant departures from Hardy-Weinberg equilibrium were detected at the D18S51, TPOX and CSF1PO loci, which persisted after applying the Bonferroni correction. Gene diversity values oscillate between 0.6302 (CSF1PO) and 0.8731 (D21S11). Observed heterozygosity (Ho) ranges from 0.2632 (D18S51) to 0.8333 (vWA) and is lower than the expected heterozygosity (He) for 12 of the 13 loci analyzed. The genetic relationships of the Arrernte with Middle Eastern, East Asian, South Asian and Indian populations were analyzed by distance-based methods, including Neighbor-Joining trees and nonmetric multidimensional scaling. In addition, the genetic contribution of the populations included in the analysis to the Arrernte gene pool was estimated utilizing weighted least square coefficients. Although the Arrernte population exhibits a remarkable level of genetic differentiation, results of the phylogeographic analyses based on autosomal microsatellite data suggest a certain degree of genetic relatedness between the Arrernte tribe of Australia and populations from the Indian subcontinent. In contrast, the STR diversity analyses failed to detect substantial East Asian contribution to the genetic background of the Arrernte group.

Characterization of immunophilins in the silkmoth Bombyx mori.

The FK506-binding proteins (FKBPs) perform an extensive variety of functions in numerous organisms from archaea to humans. The FKBPs are distinguished by their peptidyl-prolyl cis-trans isomerase (PPIase) activity and ability to bind the immunosuppressive drugs FK506 and rapamycin. Here, we report the isolation and characterization of FKBP45, a novel member of the FKBP family obtained from U1 small nuclear RNA (snRNA) binding assays using Bombyx mori nuclear extracts. The protein, an apparent orthologue of FKBP46 from the armyworm, Spodoptera frugiperda, was found to associate with U1 stem-loop I RNA in vitro. The FKBP45 cDNA was isolated and the genomic sequence was characterized, including the positions of exon/intron junctions and consensus splice sites. Using bioinformatics, transcription factor consensus binding sites were identified and subsequent Western blotting from developing eggs indicate that FKBP45 is differentially expressed during embryogenesis. A database was assembled using more than 1,800 available FKBP amino acid sequences and pairwise sequence alignments revealed several putative FKBP45 orthologues in various species. Analysis of these sequences revealed the position of an RNA binding domain within this new protein. In addition, FKBP45 possesses similar characteristics to several potential orthologues, including the presence of bipartite nuclear localization signals (NLSs) and phosphorylation sites.

Male amelogenin dropouts: phylogenetic context, origins and implications.

Several commercial PCR multiplex kits incorporate the amelogenin locus for the purpose of human gender identification. Consequently, erroneous results in the electropherogram profile of this locus can carry important forensic implications. In this study, dropout of the amelogenin Y allele was detected in 5 out of 77 phenotypically normal Kathmandu males using the AmpFlSTR Identifiler kit. A battery of male-specific markers including SNPs, STRs, STSs, and a minisatellite were amplified for the five amelogenin null samples in order to delineate the breakpoints of the deletions as well as assess the overall integrity of the Y-chromosome. This study represents the first to examine the haplogroup affiliation of the AMGY deletions. The analyses performed suggest a single origin for the five deletions as indicated by their allocation to a specific Y-haplogroup (J2b2-M241), related Y-STR haplotypes and identical regional localization of breakpoints. The age estimated from the microsatellite variation for the amelogenin deletions (if they are associated by descent) is approximately 6.5+/-3.3 ky, younger than the previously reported related age of the M241 haplogroup representatives (13-14 ky). Our data in combination with previous publications suggest a concentration of afflicted individuals in the Indian subcontinent, possibly as a result of common ancestry. The elevated incidence of the amelogenin dropout in these populations accentuates the need to utilize other loci for gender determination in order to obtain an accurate set of inclusion criteria in forensic casework.

Polymorphic Alu insertions among Mayan populations.

The Mayan homeland within Mesoamerica spans five countries: Belize, El Salvador, Guatemala, Honduras and Mexico. There are indications that the people we call the Maya migrated from the north to the highlands of Guatemala as early as 4000 B.C. Their existence was village-based and agricultural. The culture of these Preclassic Mayans owes much to the earlier Olmec civilization, which flourished in the southern portion of North America. In this study, four different Mayan groups were examined to assess their genetic variability. Ten polymorphic Alu insertion (PAI) loci were employed to ascertain the genetic affinities among these Mayan groups. North American, African, European and Asian populations were also examined as reference populations. Our results suggest that the Mayan groups examined in this study are not genetically homogeneous.

Iran: tricontinental nexus for Y-chromosome driven migration.

Due to its pivotal geographic position, present day Iran likely served as a gateway of reciprocal human movements. However, the extent to which the deserts within the Iranian plateau and the mountain ranges surrounding Persia inhibited gene flow via this corridor remains uncertain. In order to assess the magnitude of this region's role as a nexus for Africa, Asia and Europe in human migrations, high-resolution Y-chromosome analyses were performed on 150 Iranian males. Haplogroup data were subsequently compared to regional populations characterized at similar phylogenetic levels. The Iranians display considerable haplogroup diversity consistent with patterns observed in populations of the Middle East overall, reinforcing the notion of Persia as a venue for human disseminations. Admixture analyses of geographically targeted, regional populations along the latitudinal corridor spanning from Anatolia to the Indus Valley demonstrated contributions to Persia from both the east and west. However, significant differences were uncovered upon stratification of the gene donors, including higher proportions from central east and southeast Turkey as compared to Pakistan. In addition to the modulating effects of geographic obstacles, culturally mediated amalgamations consistent with the diverse spectrum of a variety of historical empires may account for the distribution of haplogroups and lineages observed. Our study of high-resolution Y-chromosome genotyping allowed for an in-depth analysis unattained in previous studies of the area, revealing important migratory and demographic events that shaped the contemporary genetic landscape.

Iranian STR variation at the fringes of biogeographical demarcation.

The integrative relationship between population genetics and forensic biology allows for a thorough genetic characterization of extant human populations. This study aimed to genetically characterize 150 unrelated healthy donors from a general population in Iran both forensically and phylogenetically. The allelic frequencies of 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were generated. This constitutes the core of polymerase chain reaction (PCR)-based DNA genetic markers in the US Combined DNA Index System (CODIS) plus two additional loci (D2S1338 and D19S433) that together are consistent with several other worldwide database requirements. There were no deviations from Hardy-Weinberg expectations. Based upon the allelic frequencies, several important forensic parameters were calculated including: gene diversity (GD) index, power of discrimination (PD), polymorphic information content (PIC) and power of exclusion (PE). G-tests indicate the allelic frequencies of the Iranians are statistically non-significant compared to two Turkish populations yet, statistically different from the remaining 18 groups obtained from the literature and examined in this study. This suggests that the Iranian dataset may be forensically equivalent to the dataset from the Turkish region of Eastern Anatolia and the general population from Turkey. Phylogenetic analysis of our population with the full set of 15 loci indicate the Iranians occupy an intermediate position relative to the major Caucasian and East Asian clades on a global level. A regional phylogenetic analysis using 13 of the 15 loci indicate the Iranians segregate in a more compact association with groups from southeastern Spain, Arabs from Morocco and Syria, and especially with the general population from Turkey and those from Eastern Anatolia. These groups are flanked by highly differentiated populations from northern India and a Berber group from Tunisia on opposing ends of the regional phylogram. This report also demonstrates the necessity to thoroughly characterize the genetic composition of populations located in geographic intersections in order to choose the appropriate dataset on which to base forensic calculations, not only at an intra-population level, but also at an inter-population level as well.

Allelic frequencies of 13 STR loci in autochthonous Basques from the province of Vizcaya (Spain).

Allelic frequencies of 13 STR loci (D3S1358, VWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D16S539, TH01, TPOX, CSF1PO, and D7S820) were estimated from a sample of 73 unrelated healthy donors natives of the Spanish Basque province of Vizcaya. These STR loci constitute the core of polymerase chain reaction (PCR)-based DNA genetic markers in the US Combined DNA Index System (CODIS). All STR loci analysed met Hardy-Weinberg expectations. Based upon the allelic frequencies, forensically important parameters including gene diversity (GD), polymorphism information content (PIC) and power of discrimination (PD) were calculated.

Phylogenetic information in polymorphic L1 and Alu insertions from East Asians and Native American populations.

This study attempts to ascertain genetic affinities between Native American and East Asian populations by analyzing four polymorphic Alu insertions (PAIs) and three L1 polymorphic loci. These two genetic systems demonstrated strong congruence when levels of diversity and genetic distances were considered. Overall, genetic relatedness within Native American groups does not correlate with geographical and linguistic structure, although strong grouping for Native Americans with East Asians was demonstrated, with clear discrimination from African and European groups. Most of the variation was assigned to differences occurring within groups, but the interpopulation variation found for South Amerindians was recognizably higher in comparison to the other sampled groups of populations. Our data suggest that bottleneck events followed by strong influence of genetic drift in the process of the peopling of the Americas may have been determinant factors in delineating the genetic background of present-day South Amerindians. Since no clear subgroups were detected within Native Americans and East Asians, there is no indication of multiple waves in the early colonization of the New World.

Autosomal STR variation in five Austronesian populations.

Human population characteristics at the genetic level are integral to both forensic biology and population genetics. This study evaluates biparental microsatellite markers in five Austronesian-speaking groups to characterize their intra- and interpopulation differences. Genetic diversity was analyzed using 15 short tandem repeat (STR) loci from 338 unrelated individuals from 5 Pacific islands populations, including the aboriginal Ami and Atayal groups from Taiwan, Bali and Java in Indonesia, and the Polynesian islands of Samoa. Allele frequencies from the STR profiles were determined and compared to other geographically targeted worldwide populations procured from recent literature. Hierarchical AMOVA analysis revealed a large number of loci that exhibit significant correspondence to linguistic partitioning among groups of populations. A pronounced divide exists between Samoa and the East (Formosa) and Southeast Asian (Bali and Java) islands. This is clearly illustrated in the topology of the neighbor-joining tree. Phylogenetic analyses also indicate clear distinctions between the Ami and Atayal and between Java and Bali, which belie the respective geographic proximities of the populations in each set. This differentiation is supported by the higher interpopulation variance components of the Austronesian populations compared to other Asian non-Austronesian groups. Our phylogenetic data indicate that, despite their linguistic commonalities, these five groups are genetically distinct. This degree of genetic differentiation justifies the creation of population-specific databases for human identification.

Variants of U1 small nuclear RNA assemble into spliceosomal complexes.

In this study, the existence of additional U1 snRNA variants in the posterior silk gland of the Bombyx mori Nistari strain from India was investigated. Three new U1 variants were detected. One of the new isoforms (U1 SG1) was found to be preferentially assembled into high molecular weight spliceosomal complexes in comparison with the total cellular lysate RNA control. Structural and nucleotide differences were examined in these new isoforms and compared with the previously reported U1 variants. Free energy (Delta G) values for the entire U1 snRNA secondary structures as well as the individual stem/loops (I, II, III and IV) domains of the isoforms were estimated to determine their structural stability.

The Levant versus the Horn of Africa: evidence for bidirectional corridors of human migrations.

Paleoanthropological evidence indicates that both the Levantine corridor and the Horn of Africa served, repeatedly, as migratory corridors between Africa and Eurasia. We have begun investigating the roles of these passageways in bidirectional migrations of anatomically modern humans, by analyzing 45 informative biallelic markers as well as 10 microsatellite loci on the nonrecombining region of the Y chromosome (NRY) in 121 and 147 extant males from Oman and northern Egypt, respectively. The present study uncovers three important points concerning these demic movements: (1) The E3b1-M78 and E3b3-M123 lineages, as well as the R1*-M173 lineages, mark gene flow between Egypt and the Levant during the Upper Paleolithic and Mesolithic. (2) In contrast, the Horn of Africa appears to be of minor importance in the human migratory movements between Africa and Eurasia represented by these chromosomes, an observation based on the frequency distributions of E3b*-M35 (no known downstream mutations) and M173. (3) The areal diffusion patterns of G-M201, J-12f2, the derivative M173 haplogroups, and M2 suggest more recent genetic associations between the Middle East and Africa, involving the Levantine corridor and/or Arab slave routes. Affinities to African groups were also evaluated by determining the NRY haplogroup composition in 434 samples from seven sub-Saharan African populations. Oman and Egypt's NRY frequency distributions appear to be much more similar to those of the Middle East than to any sub-Saharan African population, suggesting a much larger Eurasian genetic component. Finally, the overall phylogeographic profile reveals several clinal patterns and genetic partitions that may indicate source, direction, and relative timing of different waves of dispersals and expansions involving these nine populations.

A diversity of U1 small nuclear RNAs in the silk moth Bombyx mori.

Variants of U1 small nuclear RNAs (snRNAs) have been previously detected in a permanent cell line (BmN) of the silk moth Bombyx mori. In this study, the existence of U1 snRNA isoforms in the silk gland (SG) of the organism is investigated. The polyploidy (approximately 200,000X the 2N somatic value) state of the B. mori silk gland cells represents a unique system to explore the potential presence and differential expression of multiple U1 variants in a normal tissue. B. mori U1-specific RT-PCR libraries from the silk gland were generated and five U1 isoforms were isolated and characterized. Nucleotide differences, structural alterations, as well as protein and RNA interaction sites were examined in these variants and compared to the previously reported isoforms from the transformed BmN cell line. In all these SG U1 variants, variant sites and inter-species differences are located in moderately conserved regions. Substitutional or compensatory changes were found in the double stranded areas and clustered in moderately conserved regions. Some of the changes generate stronger base pairing. Calculated free energy (DeltaG) values for the entire U1 snRNA secondary structures and for the individual stem/loops (I, II, III and IV) domains of the isoforms were generated and compared to determine their structural stability. Using phylogenetic analysis, an evolutionary parallelism is observed between the polymorphic sites in B. mori and variant locations found among animal and plant species.

Multiple forms of U2 snRNA coexist in the silk moth Bombyx mori.

Eight U2 snRNA variants were isolated from several Bombyx mori U2-specific RT-PCR libraries. U2 sequences and secondary structures were generated and examined in terms of potential RNA and protein interactions. Analysis indicated that nucleotide changes occurred in both stem/loop and single-stranded areas. Changes in the double stranded areas were either compensatory, single substitutions (e.g. C <--> U) or prevented the double-stranded formation of one or two base pairs. The polymorphisms were clustered in moderately conserved regions. Some of the changes observed generated stronger base pairing. Inter-species conserved protein or RNA-binding sites were relatively unaffected. No polymorphic sites were found in known functional sequences. Bombyx mori and Drosophila melanogaster U2 sequences are 95% and 70% similar at the 5'- and the 3'-ends of the molecule, respectively. Phylogenetic analysis of the U2 sequences demonstrates remarkable conservation across species.