title: Meta-Analysis of Mitochondrial DNA Variation in the Iberian Peninsula.
abstract: The Iberian Peninsula has been the focus of attention of numerous studies dealing with mitochondrial DNA (mtDNA) variation, most of them targeting the control region segment. In the present study we sequenced the control region of 3,024 Spanish individuals from areas where available data were still limited. We also compiled mtDNA haplotypes from the literature involving 4,588 sequences and 28 population groups or small regions. We meta-analyzed all these data in order to shed further light on patterns of geographic variation, taking advantage of the large sample size and geographic coverage, in contrast with the atomized sampling strategy of previous work. The results indicate that the main mtDNA haplogroups show primarily clinal geographic patterns across the Iberian geography, roughly along a North-South axis. Haplogroup HV0 (where haplogroup U is nested) is more prevalent in the Franco Cantabrian region, in good agreement with previous findings that identified this area as a climate refuge during the Last Glacial Maximum (LGM), prior to a subsequent demographic re-expansion towards Central Europe and the Mediterranean. Typical sub-Saharan and North African lineages are slightly more prevalent in South Iberia, although at low frequencies; this pattern has been shaped mainly by the transatlantic slave trade and the Arab invasion of the Iberian Peninsula. The results also indicate that summary statistics that aim to measure molecular variation, or AMOVA, have limited sensitivity to detect population substructure, in contrast to patterns revealed by phylogeographic analysis. Overall, the results suggest that mtDNA variation in Iberia is substantially stratified. These patterns might be relevant in biomedical studies given that stratification is a common cause of false positives in case-control mtDNA association studies, and should be also considered when weighting the DNA evidence in forensic casework, which is strongly dependent on haplotype frequencies.
authors.affiliation: Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.|GenPop Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago, Galicia, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Barral-Arca
authors.affiliation: Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.|GenPop Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago, Galicia, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Pischedda
authors.affiliation: Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.|GenPop Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago, Galicia, Spain.|Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría (GENVIP), Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gómez-Carballa
authors.affiliation: Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Pastoriza
authors.affiliation: Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Mosquera-Miguel
authors.affiliation: Servicio de Biología, Instituto Nacional de Toxicología y Ciencias Forenses, Departamento de Sevilla, Sevilla, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: López-Soto
authors.affiliation: Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría (GENVIP), Hospital Clínico Universitario and Universidade de Santiago de Compostela (USC), Galicia, Spain.|Pediatric Emergency and Critical Care Division, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Martinón-Torres
authors.affiliation: Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Álvarez-Iglesias
authors.affiliation: Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.|GenPop Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago, Galicia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics*; D030541:Databases, Genetic; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial