A GEP-ISFG collaborative study on the optimization of an X-STR decaplex: data on 15 Iberian and Latin American populations

Abstract In a collaborative work carried out by the Spanish and Portuguese ISFG Working Group (GEPISFG), a polymerase chain reaction multiplex was optimized in order to type ten X-chromosome short tandem repeats (STRs) in a single reaction, including: DXS8378, DXS9902, DXS7132, DXS9898, DXS6809, DXS6789 DXS7133, GATA172D05, GATA31E08, and DXS7423. Using this X-decaplex, each 17 of the participating laboratories typed a population sample of approximately 200 unrelated individuals (100 males and 100 females). In this work, we report the allele frequencies for the ten XSTRs in 15 samples from Argentina (Buenos Aires, Córdoba, Río Negro, Entre Ríos, and Misiones), Brazil (São Paulo, Rio de Janeiro, Paraná, and Mato Grosso do Sul), Colombia (Antioquia), Costa Rica, Portugal (Northern and Central regions), and Spain (Galicia and Cantabria). Gene diversities were calculated for the ten markers in each population and all values were above 56%. The average diversity per locus varied between 66%, for DXS7133, and 82%, for DXS6809. For this set of STRs, a high discrimination power was obtained in all populations, both in males (≥1 in 5×105) and females (≥1 in 3×109), as well as high mean exclusion chance in father/daughter duos (≥99.953%) and in father/mother/daughter trios (≥99.999%). Genetic distance analysis showed no significant differences between northern and central Portugal or between the two Spanish samples from Galicia and Cantabria. Inside Brazil, significant differences were found between Rio de Janeiro and the other three populations, as well as between São Paulo and Paraná. For the five Argentinean samples, significant distances were only observed when comparing Misiones with Entre Ríos and with Río Negro, the only two samples that do not differ significantly from Costa Rica. Antioquia differed from all other samples, except the one from Río Negro.Fil: Gusmão, Leonor. Universidad de Porto; PortugalFil: Sánchez Diz, Paula. Universidad de Santiago de Compostela; EspañaFil: Alves, Cíntia. Universidad de Porto; PortugalFil: Gomes, Iva. Universidad de Porto; PortugalFil: Zarrabeitia, María Teresa. Universidad de Cantabria; EspañaFil: Abovich, Mariel. Ministerio de Ciencia, Tecnología e Innovación Productiva. Banco Nacional de Datos Genéticos; ArgentinaFil: Atmetlla, Ivannia. Laboratorio de Análisis Clínicos y Moleculares; Costa RicaFil: Bobillo, Maria Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Bravo, Luisa. Laboratorio Genes; ColombiaFil: Builes, Juan. Laboratorio Genes; ColombiaFil: Cainé, Laura. Instituto Nacional de Medicina Legal; PortugalFil: Calvo, Raquel. Universidad de Santiago de Compostela; EspañaFil: Carvalho, Elizeu. Universidade do Estado do Rio de Janeiro; BrasilFil: Carvalho, Mónica. Instituto Nacional de Medicina Legal; PortugalFil: Cicarelli, Regina. Universidade Estadual Paulista; BrasilFil: Catelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Espinoza, Marta. Unidad de Genética Forense; Costa RicaFil: García Monasterio, Óscar. Area de Laboratorio Ertzaintza; EspañaFil: Malaghini, Marcelo. Laboratorio Frischmann Aisengart ; BrasilFil: Martins, Joyce. Universidade Estadual Paulista; BrasilFil: Pinheiro, Fátima. Instituto Nacional de Medicina Legal; PortugalFil: Porto, Maria João. Instituto Nacional de Medicina Legal; PortugalFil: Raimondi, Eduardo Humberto. Fundación Favaloro; ArgentinaFil: Riancho, Jose Antonio. Universidad de Cantabria; EspañaFil: Rodríguez, Amelia. Universidad de Santiago de Compostela; EspañaFil: Rodríguez, Anayanci. Universidad de Santiago de Compostela; EspañaFil: Rodríguez Cardozo, Belén. Ministerio de Ciencia, Tecnología e Innovación Productiva. Banco Nacional de Datos Genéticos; ArgentinaFil: Schneider, Vicente. Laboratorio Frischmann Aisengart; BrasilFil: Silva, Sandra. Laboratorio de Análisis Clínicos y Moleculares; Costa RicaFil: Tavares, Celso. Universidade do Estado do Rio de Janeiro; BrasilFil: Toscanini, Ulises Faustino. Fundación Favaloro; ArgentinaFil: Vullo, Carlos. No especifíca;Fil: Whittle, Martin. Genomic Engenharia Molecular; BrasilFil: Yurrebaso, Iñaki. Laboratorio Ertzaintza; EspañaFil: Carracedo, Ángel. Universidad de Santiago de Compostela; EspañaFil: Amorim, António. Universidad de Porto; Portuga

New Population and Phylogenetic Features of the Internal Variation within Mitochondrial DNA Macro-Haplogroup R0

BACKGROUND: R0 embraces the most common mitochondrial DNA (mtDNA) lineage in West Eurasia, namely, haplogroup H (approximately 40%). R0 sub-lineages are badly defined in the control region and therefore, the analysis of diagnostic coding region polymorphisms is needed in order to gain resolution in population and medical studies. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the first hypervariable segment (HVS-I) of 518 individuals from different North Iberian regions. The mtDNAs belonging to R0 (approximately 57%) were further genotyped for a set of 71 coding region SNPs characterizing major and minor branches of R0. We found that the North Iberian Peninsula shows moderate levels of population stratification; for instance, haplogroup V reaches the highest frequency in Cantabria (north-central Iberia), but lower in Galicia (northwest Iberia) and Catalonia (northeast Iberia). When compared to other European and Middle East populations, haplogroups H1, H3 and H5a show frequency peaks in the Franco-Cantabrian region, declining from West towards the East and South Europe. In addition, we have characterized, by way of complete genome sequencing, a new autochthonous clade of haplogroup H in the Basque country, named H2a5. Its coalescence age, 15.6+/-8 thousand years ago (kya), dates to the period immediately after the Last Glacial Maximum (LGM). CONCLUSIONS/SIGNIFICANCE: In contrast to other H lineages that experienced re-expansion outside the Franco-Cantabrian refuge after the LGM (e.g. H1 and H3), H2a5 most likely remained confined to this area till present days

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Data from: Genetic uniqueness of the Waorani tribe from the Ecuadorian Amazon

South America and especially the Amazon basin is known to be home to some of the most isolated human groups in the world. Here we report on a study of mitochondrial DNA (mtDNA) in the Waorani from Ecuador, probably the most warlike human population known to date. Seeking to look in more depth at the characterization of the genetic diversity of this Native American tribe, molecular markers from the X and Y chromosomes were also analyzed. Only three different mitochondrial DNA haplotypes were detected among the Waorani sample. One of them, assigned to Native American haplogroup A2, accounted for more than 94% of the total diversity of the maternal gene pool. Our results for sex chromosome molecular markers failed to find direct kinship between individuals and further emphasized the low genetic diversity of the mtDNA found. Bearing in mind the results obtained for both the analysis of the mtDNA control region and complete mitochondrial genomes, we suggest the existence of a "Waorani-specific" mtDNA lineage. According to current knowledge on the phylogeny of haplogroup A2, we propose that this lineage could be designated as subhaplogroup A2s. Its wide predominance among the Waorani people might have been conditioned by severe genetic drift episodes resulting from founding events, long-term isolation, and a traditionally small population size most likely associated with the striking ethnography of this Amazonian community. In all, the Waorani constitute a fine example of how genetic imprint may mirror ethnopsychology and sociocultural features in human populations

Cardosoetal_Waorani_Suppl_S3

Female genotypes and male haplotypes for 10 X-chromosome STRs in a Waorani population sampl

Results of the GEP-ISFG collaborative study on two Y-STRs tetraplexes

Abstract A collaborative exercise was carried out by the Spanish and Portuguese ISFG Working Group (GEP-ISFG) in order to evaluate the performance of two Y-chromosome STR PCR tetraplexes, which include the loci DYS461, GATA C4, DYS437 and DYS438 (GEPY I), and DYS460, GATA A10, GATA H4 and DYS439 (GEPY II). The participating laboratories were asked to type three samples for the eight markers, using a specific amplification protocol. In addition, two control samples, with known haplotypes, were provided. The results obtained by the 13 different participating laboratories were identical, except for two laboratories that failed to type correctly the same two samples for GATA C4. By sequence analyses, two different GATA C4 allele structures were found. One control sample (allele 21) and two questioned samples (allele 22, correctly typed by all the laboratories, and allele 25) presented the following repeat structure: (TCTA) 4 (TGTA) 2 (TCTA) 2 (TGTA) 2 (TCTA) n , but different from the one found for allele 26 in one sample included in this exercise, as well as in the second control sample (allele 23), namely (TCTA) 4 (TGTA) 2 (TCTA) 2 (TGTA) 2 (TCTA) 2 (TGTA) 2 -(TCTA) n . The collaborative exercise results proved that both Y-tetraplexes produce good amplification results, with the advantage of being efficiently typed using different separation and detection methodologies. However, since GATA C4 repeat presents a complex structure, with alleles differing in sequence structure, efficient denaturing conditions should be followed in order to avoid typing errors due to sizing problems.

Cumulative genetic score and C9orf72 repeat status independently contribute to amyotrophic lateral sclerosis risk in 2 case-control studies

Background and Objectives Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores. Methods Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion. Final cohort size was 219 ALS and 223 healthy controls after genotyping and participant filtering. Polygenic scores excluding the C9 region were generated using an independent ALS genome-wide association study (20,806 cases, 59,804 controls). Adjusted logistic regression and receiver operating characteristic curves evaluated the association and classification between polygenic scores and ALS status, respectively. Population attributable fractions and pathway analyses were conducted. An independent Spanish study sample (548 cases, 2,756 controls) was used for replication. Results Polygenic scores constructed from 275 single-nucleotide variation (SNV) had the best model fit in the Michigan cohort. An SD increase in ALS polygenic score associated with 1.28 (95% CI 1.04-1.57) times higher odds of ALS with area under the curve of 0.663 vs a model without the ALS polygenic score (p value = 1 × 10-6). The population attributable fraction of the highest 20th percentile of ALS polygenic scores, relative to the lowest 80th percentile, was 4.1% of ALS cases. Genes annotated to this polygenic score enriched for important ALS pathomechanisms. Meta-analysis with the Spanish study, using a harmonized 132 single nucleotide variation polygenic score, yielded similar logistic regression findings (odds ratio: 1.13, 95% CI 1.04-1.23). Discussion ALS polygenic scores can account for cumulative genetic risk in populations and reflect disease-relevant pathways. If further validated, this polygenic score will inform future ALS risk modelsFunding: National ALS Registry/CDC/ATSDR (1R01TS000289); National ALS Registry/CDC/ATSDR CDCP-DHHS-US (CDC/ATSDR 200-2013-56856); NIEHS K23ES027221; NIEHS R01ES030049; NINDS R01NS127188, ALS Association (20-IIA-532), the Dr. Randall W. Whitcomb Fund for ALS Genetics, the Peter R. Clark Fund for ALS Research, the Scott L. Pranger ALS Clinic Fund, and the NeuroNetwork for Emerging Therapies at the University of Michigan. This work was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (Z01-AG000949-02). Project “ALS Genetic study in Madrid Autonomous Community” funded by “ESTRATEGIAS FRENTE A ENFERMEDADES NEURODEGENERATIVAS

A GEP-ISFG collaborative study on the optimization of an X-STR decaplex: data on 15 Iberian and Latin American populations

Abstract In a collaborative work carried out by the Spanish and Portuguese ISFG Working Group (GEP-ISFG), a polymerase chain reaction multiplex was optimized in order to type ten X-chromosome short tandem repeats (STRs) in a single reaction, including: DXS8378, DXS9902, DXS7132, DXS9898, DXS6809, DXS6789, DXS7133, GATA172D05, GATA31E08, and DXS7423. Using this X-decaplex, each 17 of the participating laboratories typed a population sample of approximately 200 unrelated individuals (100 males and 100 females). In this work, we report the allele frequencies for the ten XSTRs in 15 samples from Argentina (Buenos Aires, Int J Legal Me