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We are at the dawn of the efforts to describe and understand the origins of genetic diversity in Argentina from high-throughput data. This knowledge is a primary step in the intent of deciphering the specific genetic bases of diseases and drug response in the country. Similarly to other populations across the Americas, genetic ancestry in Argentinean populations traces back into African, European and Native American ancestors, reflecting a complex demographic history with multiple migration and admixture events in pre- and post-colonial times. However, little is known about the sub-continental origins of these three main ancestries. We present new high-throughput genotyping data for 87 admixed individuals across Argentina. This data was combined to previously published data for admixed individuals in the region and then compared to different reference panels specifically built to run population structure analyses at a sub-continental level. Concerning the European and African ancestries, we confirmed previous results about their main origins, and we provide new insights into the presence of other origins that reflect historical records. As for the Native American ancestry, leveraging genotype data for archeological samples in the region in order to gain temporal depth in our analyses, we could identify four Native American components segregating in modern Argentinean populations . Three of them are also found in modern South American populations and are specifically represented in Central Chile/Patagonia, Lowlands and Central Andes geographic areas. The fourth one may be specific to the Central Western region of Argentina. Identifying such component has not been straightforward since it is not well represented in any genomic data from the literature. Altogether, we provide useful insights into the multiple population groups from different continents that have contributed to present-days genetic diversity in Argentina. We encourage the generation of massive genotype data locally to further describe the genetic structure in Argentina., Facultad de Ciencias Naturales y Museo, Instituto Multidisciplinario de Biología Celular

El Gran Chaco es uno de los biomas de las Tierras Bajas sudamericanas más recientemente poblados por los seres humanos, ha mantenido su diversidad etnolingüística y muestra evidencias de la existencia de contactos interétnicos. El objetivo de este trabajo es reconocer estructuración genética en la fracción nativa de los linajes paternos en las poblaciones chaqueñas, para lo cual se analizaron 116 individuos de poblaciones wichi, toba, chorote y mocoví de Argentina y lengua y ayoreo de Paraguay. Se identificaron los haplogrupos paternos a través de AFLP y posteriormente se determinaron los haplotipos basados en 17 microsatélites del cromosoma Y en los individuos poseedores de linajes nativos. Se agregaron 166 individuos del NOA para comparaciones regionales. Se estimaron frecuencias haplotípicas e índices de fijación. Se construyeron redes medianas y se evaluó la correlación entre las distancias geográficas y genéticas. Se realizaron Análisis de Coordenadas Principales, y se calcularon las posibles barreras genéticas (áreas geográficas donde la diferenciación genética entre poblaciones adyacentes es mayor). Se obtuvieron 167 haplotipos únicos y 43 haplotipos compartidos para las poblaciones de Gran Chaco y NOA. Las distancias FST y el análisis de autocorrelación espacial muestran estructura geográfica de aislamiento por distancia y 3 barreras que separan a tobas de Salta, lengua y ayoreo de Paraguay y mocovíes de Chaco, esperable ya que estas dos últimas son poblaciones que están geográficamente más distantes. Al agregar las muestras del NOA las barreras antes encontradas se mantienen, pero no se evidencian barreras entre las poblaciones de NOA y Gran Chaco, sugiriendo conexiones entre ambas regiones., Gran Chaco is one of the most recently peopled areas from the South American Lowlands; it has kept its ethnolinguistic diversity and shows evidence of interethnic contacts. The goal of this paper is to describe the structure of native male lineages in Gran Chaco populations, for which we analyzed 116 individuals from wichi, toba, chorote, mocoví populations in Argentina and lengua and ayoreo populations from Paraguay. We identified paternal haplogroups by AFLP and haplotypes based on 17 microsatellites. We added to the analyses 166 individuals from the Argentinian Northwest (NOA) for regional comparisons. We estimated haplotypic frequencies and fixation indexes and assessed the correlation between geographic and genetic distances. We performed Principal Coordinates Analysis and calculated possible genetic barriers. We found 167 unique haplotypes, 43of which were shared between the Gran Chaco and NOA populations. FST distances and Autocorrelation Analysis show a geographic pattern of isolation by distance and 3 barriers that segregate the toba from Salta, lengua and ayoreo from Paraguay and the mocovi from Chaco, which is expected since these last two populations are geographically more distant. These barriers persist when the Argentinian Northwest samples are added, but there is no evidence of barriers between the Gran Chaco and Northwest populations, suggesting connections between these two regions., O Grande Chaco é um dos biomas das Terras Baixas sul-americanas mais recentemente povoado pelos seres humanos, tem mantido sua diversidade etnolinguística e apresenta evidências da existência de contatos interétnicos. O objetivo deste trabalho é reconhecer estruturação genética na fração nativa das linhagens paternas nas populações do Chaco, para o qual foram analisados 116 indivíduos das populações wichi, toba, chorote e mocoví da Argentina, e lengua e ayoreo do Paraguai. Foram identificados os haplogrupos paternos por meio de AFLP e, posteriormente, foram determinados os haplótipos baseados em 17 microssatélites do cromossomo Y nos indivíduos possuidores de linhagens nativas. Foram adicionados 166 indivíduos do NOA para comparações regionais. As frequências dos haplótipos e os índices de fixação foram estimados. Redes medianas foram construídas e a correlação entre as distâncias geográficas e genéticas foi avaliada. Foram realizadas Análises de Coordenadas Principais, e calculadas as possíveis barreiras genéticas (áreas geográficas onde a diferenciação genética entre populações adjacentes é maior). Foram obtidos 167 haplótipos únicos e 43 haplótipos compartilhados para as populações do Grande Chaco e NOA. As distâncias FST e a análise de autocorrelação espacial mostram estrutura geográfica de isolamento por distância e 3 barreiras que separam os tobas de Salta, lengua e ayoreo do Paraguai e os mocovís do Chaco, o que é esperado visto que estas duas últimas são populações que estão geograficamente mais distantes. Quando as amostras do NOA foram adicionadas, as barreiras encontradas anteriormente foram mantidas, mas nenhuma barreira foi evidenciada entre as populações do NOA e do Grande Chaco, sugerindo conexões entre as duas regiões., Dossier: Contribuciones antropológicas a la comprensión del pasado en el Gran Chaco sudamericano., Facultad de Ciencias Naturales y Museo

En las sociedades con transmisión paterna de los apellidos, la distribución de los mismos debería seguir el mismo recorrido que los linajes del cromosoma Y. Se evalúa esta hipótesis mediante la definición de haplotipos de microsatélites del cromosoma Y en ciento setenta y cinco individuos del Noroeste Argentino, que abarcan noventa y cinco apellidos. Se compararon estas dos fuentes de información, buscando concordancias entre y dentro de apellidos, trazando redes medianas, estimando el tiempo de divergencia y comparando los resultados obtenidos con la base de datos internacional YHRD. Se establecieron dos haplotipos nodales, uno nativo americano y otro de origen europeo, rodeados por el resto de los haplotipos. En un solo caso se encontró concordancia entre apellidos y los perfiles establecidos mediante microsatélites del cromosoma Y, y también se reconocieron linajes genéticos que involucraban diferentes apellidos. A su vez, para definir si las divergencias se debían a polifiletismo o a mutaciones recientes, se estimó la distancia temporal entre las muestras del mismo apellido y haplogrupo, encontrando que en cerca de la mitad de estos casos esta profundidad temporal excedía el origen de los apellidos. Estos datos sugieren que la transmisión irregular del apellido en el Noroeste Argentino fue más elevada que aquella encontrada en otros países. Asimismo, las similitudes entre ambos tipos de linajes no debe ser dada por sentado.

Non-syndromic cleft lip with or without cleft palate (NSCLP) is a congenital malformation that shows the characteristics of a multifactorial pathology. In order to describe the genetic predisposition to this disorder, NAT genes were analyzed with special interest since they codify for N-acetyltransferases, the enzymes responsible for the biotransformation of arylamines, hydrazine drugs and a great number of toxins and carcinogens present in diet, cigarette smoke and the environment. The allelic transmission of NAT2 that determines the slow acetylator phenotype in 174 trios (case-mother/father) from ECLAMC (Latin American Collaborative Study of Congenital Malformations) maternities in Argentina was evaluated. The *4, *5B, *6, and *7 variants by PCR-RFLP were analyzed. A higher risk for the 5B*5B* genotypes (OR=2. 24; p=0.050) was found, at the expense of the cases from Patagonia, without the influence of the maternal genotype., El labio leporino con o sin paladar hendido (NSCLP) es una malformación congénita que presenta las características de una patología multifactorial. Se consideran de especial interés los genes NAT que codifican para las Nacetiltransferasas, enzimas responsables de la biotransformación de arilaminas, fármacos de hidrazina, y de un gran número de toxinas y carcinógenos presentes en la dieta, el humo de cigarro y el medio ambiente. Lo expuesto anteriormente ha despertado la sospecha de un posible rol de NAT2 en la manifestación de LL/PH en el recién nacido expuesto. En este trabajo se ha evaluado la transmisión alélica de variantes que determinan el fenotipo acetilador lento en 174 tríos (caso, madre y/o padre) reclutados por el ECLAMC (Estudio Colaborativo Latinoamericano de Malformaciones Congénitas) en maternidades de Argentina. Se analizaron las variantes *4, *5B, *6 y *7 mediante PCR-RFLP. Se halló un riesgo mayor en los casos con genotipos 5B*5B* (OR=2,24; p=0,050), a expensas de los casos de Patagonia, sin influencia del genotipo materno., Asociación de Antropología Biológica de la República Argentina

We designed an allele-specific amplification protocol to optimize Y-chromosome SNP typing, which is an unavoidable step for defining the phylogenetic status of paternal lineages. It allows the simultaneous highly specific definition of up to six mutations in a single reaction by amplification fragment length polymorphism (AFLP) without the need of specialized equipment, at a considerably lower cost than that based on single-base primer extension (SNaPshot™) technology or PCR-RFLP systems, requiring as little as 0.5 ng DNA and compatible with the small fragments characteristic of low-quality DNA. By designation of two primers recognizing the derived and ancestral state for each SNP, which can be differentiated by size by the addition of a noncomplementary nucleotide tail, we could define major Y clades E, F, K, R, Q, and subhaplogroups R1, R1a, R1b, R1b1b, R1b1c, J1, J2, G1, G2, I1, Q1a3, and Q1a3a1 through amplification fragments that ranged between 60 and 158bp.

Surnames are a vertically transmitted cultural trait that in Argentina follows the paternal line of descent when the paternity is known. There was a lack of empirical information regarding non-paternal surname transmissions among the general population, so we performed 2,550 genealogical interviews, which included 6,954 surname passes, in different regions of this country. We compared the proportion of non-paternal transmissions between the propositus and parental generation and found no significant difference between them (p0.01). Inter-population comparisons allowed us to describe 4 regional groups. We also drew models and simulations to estimate how many generations it would take to find that only half of the population maintained the paternal transmission. The lowest proportion of non-paternal transmission was 7.3%, estimating 9 generations (between 225 and 315 years) to find that, at most, half its population keeps following the paternal transmission; the highest proportion was 23%, taking 3 generations (75-105 years). Our results show a high proportion of unrecognized paternities among the general population, a very quick loss of association between male lineages and surnames, and regional proportions with significant differences between each other.

Reduced representation sequencing methods such as genotyping-by-sequencing (GBS) enable low-cost measurement of genetic variation without the need for a reference genome assembly. These methods are widely used in genetic mapping and population genetics studies, especially with non-model organisms. Variant calling error rates, however, are higher in GBS than in standard sequencing, in particular due to restriction site polymorphisms, and few computational tools exist that specifically model and correct these errors. We developed a statistical method to remove errors caused by restriction site polymorphisms, implemented in the software package GBStools. We evaluated it in several simulated data sets, varying in number of samples, mean coverage and population mutation rate, and in two empirical human data sets (N = 8 and N = 63 samples). In our simulations, GBStools improved genotype accuracy more than commonly used filters such as Hardy-Weinberg equilibrium p-values. GBStools is most effective at removing genotype errors in data sets over 100 samples when coverage is 40X or higher, and the improvement is most pronounced in species with high genomic diversity. We also demonstrate the utility of GBS and GBStools for human population genetic inference in Argentine populations and reveal widely varying individual ancestry proportions and an excess of singletons, consistent with recent population growth.

Background: NAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, hydrazine drugs, and a great number of toxins and carcinogens present in diet, cigarette smoke, and environment. Aim: To determine the association between alleles determining slow acetylator phenotype and the risk of NSCLP. Material and Methods: We analyzed *5 (481C>T), *6 (590G>A) and *7 (857G>A) alleles which determine the slow acetylator phenotype and *4 (wild type) allele by polymerase chain reaction/restriction fragment length polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards. We evaluated the transmission disequilibrium (TDT). Results: TDT showed a positive association between allele *5 and NSCLP (odds ratio = 1,6; p = 0,03). Conclusions: The presence of *5 allele is significantly higher in cases with congenital NSCLP., Facultad de Ciencias Naturales y Museo, Instituto Multidisciplinario de Biología Celular

NAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, hydrazine drugs, and a great number of toxins and carcinogens present in diet, cigarette smoke, and environment.To determine the association between alleles determining slow acetylator phenotype and the risk of NSCLP.We analyzed *5 (481CT), *6 (590GA) and *7 (857GA) alleles which determine the slow acetylator phenotype and *4 (wild type) allele by polymerase chain reaction/restriction fragment length polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards. We evaluated the transmission disequilibrium (TDT).TDT showed a positive association between allele *5 and NSCLP (odds ratio = 1,6; p = 0,03).The presence of *5 allele is significantly higher in cases with congenital NSCLP.

We designed an allele-specific amplification protocol to optimize Y-chromosome SNP typing, which is an unavoidable step for defining the phylogenetic status of paternal lineages. It allows the simultaneous highly specific definition of up to six mutations in a single reaction by amplification fragment length polymorphism (AFLP) without the need of specialized equipment, at a considerably lower cost than that based on single-base primer extension (SNaPshot™) technology or PCR-RFLP systems, requiring as little as 0.5 ng DNA and compatible with the small fragments characteristic of low-quality DNA. By designation of two primers recognizing the derived and ancestral state for each SNP, which can be differentiated by size by the addition of a noncomplementary nucleotide tail, we could define major Y clades E, F, K, R, Q, and subhaplogroups R1, R1a, R1b, R1b1b, R1b1c, J1, J2, G1, G2, I1, Q1a3, and Q1a3a1 through amplification fragments that ranged between 60 and 158bp.

Graciela Bailliet1, Marina Muzzio1,2, Virginia Ramallo1,3, Laura S. Jurado Medina1, Emma L. Alfaro4, Jose E. Dipierri4 and Claudio M. Bravi1,2 1Instituto Multidisciplinario de Biologia Celular (IMBICE), La Plata, 2Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, La Plata, 3Universidade Federal do Rio Grande do Sul, Porto Alegre, 4Instituto de Biologia de La Altura (INBIAL), Universidad Nacional de Jujuy, Jujuy, 1,2,4Argentina 3Brazil

Dear Sirs: The letter by Dr. Athey entitled “Comments on the article, “Software for Y-Haplogroup Predictions, a Word of Caution” discusses a paper of our authoring in the present Journal [1]. Though at first glance his opinion may seem reasonable, a careful analysis reveals a series of mistakes committed by Dr. Athey. In the mentioned letter, one of the main concerns of Dr. Athey is the amount of short tandem repeats (STRs) that were analyzed. He comments that seven markers should be avoided, explaining that an increase of that amount augments the probability of assignment, stating that “With the addition of a sufficient number of markers, the prediction probability for the correct haplogroup can be ‘driven’ past 99% in nearly all cases, and this almost always occurs by the point where 20 markers have been used.” Nonetheless, he does not make reference to any sort of validation study, so said 99% must only refer to the probability of assignment his own software provides. What is more, Dr. Athey seems oblivious that our paper examined this software’s predictive values in different cutoff points, up to 95% of probability of assignment, still obtaining inadequate predictive values on said cutoff point. Twelve of our haplotypes proposed from 100% to 99.6% probability of assignment to the R1b haplogroup in the Haplogroup Predictor, while none of those samples belong to the said haplogroup. In the R haplogroup, one haplotype gives 99.8% probability to an erred haplogroup (E1b1b), while 14 give from 100% to 99.4%, assigning these samples to the R1b haplogroup, and were considered as correct predictions. Note that in these cases, the predicted haplogroup follows the nomenclature of the software, and the probability was not pooled by major branches. If the seven markers of the minimal haplotype were not a proper set, Dr. Athey’s software should not provide such high probabilities of assignment in these cases, since it misleads the user. Unfortunately, Dr. Athey’s mention that seven Y-STRs are too few occurs only in his letter; neither of the two papers of his authoring [2, 3] available at the Haplogroup Predictor’s website (http:// www.hprg.com/hapest5/) nor the software instructions (http://www.hprg.com/hapest5/page4.html) explain that the user should employ more than seven markers. Otherwise, we would not have attempted to use it. Moreover, a simple glance at recent literature where the Haplogroup Predictor was employed clearly shows that researchers do not use such high amounts of Y-STRs when they rely on the Haplogroup Predictor; for instance, Salas et al. [4] used the seven Y-STRs we did, plus DYS 385 and Petrejcikova et al. [5] only 12 Y-STRs. His statement “...indeed, the seven-marker dataset apparently resulted from a study carried out over five M. Muzzio :V. Ramallo : J. M. B. Motti :M. R. Santos : J. S. Lopez Camelo :G. Bailliet Laboratorio de Genetica Molecular Poblacional, Instituto Multidisciplinario de Biologia Celular (IMBICE), CICPBA, CCT, La Plata–CONICET, La Plata, Argentina

The weight of characters is a crucial step in different population analyses. We propose a new formula to facilitate this while establishing a scale that follows the criteria of the probability of change in each character. This method is described for drawing of median-joining networks, yet it could also be used for other methods in which the weight of the characters is required. Fil: Muzzio, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Muzzio, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; Argentina Fil: Bravi, Claudio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Bailliet, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina

Durante el año 2005, se realizaron dos viajes de campaña a comunidades Wichí cercanas a las localidades de Ingeniero Juárez y Laguna Yema (provincia de Formosa, Argentina), como parte del proyecto multidisciplinario “De las historias étnicas a la prehistoria en el Gran Chaco”. Partiendo del planteo metodológico de unidad poblacional, se obtuvieron datos genéticos en 93 muestras utilizando marcadores binarios y microsatélites del cromosoma Y, determinando haplogrupos y haplotipos masculinos. El haplogrupo Q1a3a, natural del continente americano, resultó mayoritario en ambas localidades (72,7 % y 81,6 %). Los linajes moleculares se compararon con la diversidad de apellidos registrada y las posibles vinculaciones entre las comunidades Wichís se analizaron por redes “median joining”, encontrando una variabilidad de linajes coherente con la distribución de las parcialidades del “complejo étnico Wichí” propuesto por Braunstein., During the year 2005, as part of the multidisciplinary project “Of the ethnic histories to the prehistory of the Gran Chaco”, two field trips to the wichi communities nearing the locations of Ingeniero Juarez and Laguna Yema (Formosa province, Argentina) were made. From the methodological proposal of a population unit, genetic data in 93 samples, employing binary markers and microsatellites of the Y-chromosome were obtained, determining male haplogroups and haplotypes. The Q1a3a haplogroup, native of the American continent, resulted the most common in both locations (72,7% and 81,6%). The molecular lineages were compared with the registered surname diversity and the possible links between the wichi communities were analyzed through “median joining” networks, finding a lineage variability that is reasonable given the distribution of the partialities of the “wichi ethnic complex” proposed by Braunstein., Instituto Multidisciplinario de Biología Celular

Seccio ´n Antropologia Biologica, Instituto de Ciencias Antropologicas, Facultad de Filosofia y Letras,Universidad de Buenos Aires, Buenos Aires, ArgentinaKEY WORDS Y chromosome; SNP; microsatellites; south AmericaABSTRACT We analyzed 21 paragroup Q* Y chro-mosomes from South American aboriginal and urbanpopulations. Our aims were to evaluate the phyloge-netic status, geographic distribution, and genetic diver-sity in these groups of chromosomes and compare thedegree of genetic variation in relation to Q1a3a haplo-types. All Q* chromosomes from our series and fivesamples from North American Q* presented the deri-vate state for M346, that is present upstream to M3,and determined Q1a3* paragroup. We found a restric-tive geographic distribution and low frequency ofQ1a3* in South America. We assumed that this lowfrequency could be reflecting extreme drift effects.However, several estimates of gene diversity do notsupport the existence of a severe bottleneck. The meanhaplotype diversity expected was similar to that forSouth American Q1a3* and Q1a3a (0.478 and 0.501,respectively). The analysis of previous reports fromother research groups and this study shows the high-est frequencies of Q* for the West Corner and theGrand Chaco regions of South America. At present,there is no information on whether the phylogeneticstatus of Q* paragoup described in previous reports issimilar to that of Q1a3* paragroup though our resultssupport this possibility. Am J Phys Anthropol 140:578–582, 2009.

The development of online software designed for genetic studies has been exponentially growing, providing numerous benefits to the scientific community. However, they should be used with care, since some require adjustments. The efficiency of two programs for haplogroup prediction was tested with 119 samples of known haplotypes and haplogroups from Argentine populations. Quantitative estimates of the predictive quality of both software systems were computed with the uncertainty coefficient; and sensitivity, specificity, positive, and negative likelihood ratios were also calculated to assert the reliability of both programs, showing high probabilities of assigning an incorrect haplogroup.

We report a new case of a large, homoplasmic Control Region deletion in human mitochondrial DNA. A missing 154bp fragment spanning positions 16154–16307 was found in an apparently healthy blood donor from Salta (NW Argentina) whose maternal lineage was attributable to Native American haplogroup D1. The same mutation, to the best of our knowledge, has been independently reported before only twice, in both homoplasmic and heteroplasmic states.

Y-chromosome haplogroups constructed from SNP markers of Y-specific regions have been largely used in population genetic trials. These data might also be applied to forensic studies on human populations showing multiethnic admixture. Haplogroups have evidenced differential ethnic and geographic distribution. The objective of the present report was to analyze 775 male samples for 16 Y-SNP by PCR-RFLP and to describe haplogroup frequencies in three Argentine geographic regions: Central-West (Cuyo), Center, and North-West.