Connie Mulligan | University of Florida (original) (raw)

Papers by Connie Mulligan

Marina S. Ascunce, Andrew Kitchen, Peter R. Schmidt, Michael M. Miyamoto, and Connie J. Mulligan ... more Marina S. Ascunce, Andrew Kitchen, Peter R. Schmidt, Michael M. Miyamoto, and Connie J. Mulligan (2006) An unusual pattern of ancient mitochondrial DNA haplogroups in northern African cattle. Zoological Studies 46(1): xxx-xxx. In

American Journal of Physical Anthropology

Southern Arabia and the Horn of Africa are important geographic centers for the study of human po... more Southern Arabia and the Horn of Africa are important geographic centers for the study of human population history because a great deal of migration has characterized these regions since the first emergence of humans out of Africa. Analysis of Jewish groups pro-vides a unique opportunity to investigate more recent population histories in this area. Mitochondrial DNA is used to investigate the maternal evolutionary history and can be combined with historical and linguistic data to test various population histories. In this study, we assay mitochondrial control region DNA sequence and diagnostic coding variants in Yemenite (n 5 45) and Ethiopian (n 5 41) Jewish populations, as well as in neighboring non-Jewish Yemeni (n 5 50) and Ethiopian (previously published Semitic speakers) populations. We investigate their population histories through a com-parison of haplogroup distributions and phylogenetic networks. A high frequency of sub-Saharan African L haplogroups was found in both Jewish...

Malaria journal, 2015

Haiti and the Dominican Republic, which share the island of Hispaniola, are the last locations in... more Haiti and the Dominican Republic, which share the island of Hispaniola, are the last locations in the Caribbean where malaria still persists. Malaria is an important public health concern in Haiti with 17,094 reported cases in 2014. Further, on January 12, 2010, a record earthquake devastated densely populated areas in Haiti including many healthcare and laboratory facilities. Weakened infrastructure provided fertile reservoirs for uncontrolled transmission of infectious pathogens. This situation results in unique challenges for malaria epidemiology and elimination efforts. To help Haiti achieve its malaria elimination goals by year 2020, the Laboratoire National de Santé Publique and Henry Ford Health System, in close collaboration with the Direction d'Épidémiologie, de Laboratoire et de Recherches and the Programme National de Contrôle de la Malaria, hosted a scientific meeting on "Elimination Strategies for Malaria in Haiti" on January 29-30, 2015 at the National La...

Methods in enzymology, 2005

The use of ancient DNA (aDNA) in the reconstruction of population origins and evolution is becomi... more The use of ancient DNA (aDNA) in the reconstruction of population origins and evolution is becoming increasingly common. Novel methods exist for the isolation, purification, and analysis of aDNA because these DNA templates are likely to be damaged, fragmented and?or associated with non-nucleic acid material. However, contamination of ancient specimens and DNA extracts with modern DNA is more widespread than is generally acknowledged and remains a significant problem in aDNA analysis. Studies of human aDNA are uniquely sensitive to contamination due to the continual presence of potential contamination sources. Meticulous authentication of results and careful selection of polymorphic markers capable of distinguishing between aDNA and probable DNA contaminants are critical to a successful aDNA study.

Journal of anthropological sciences = Rivista di antropologia : JASS / Istituto italiano di antropologia, 2010

Molecular Anthropology is a relatively young field of research. In fact, less than 50 years have ... more Molecular Anthropology is a relatively young field of research. In fact, less than 50 years have passed since the symposium "Classification and Human Evolution" (1962, Burg Wartenstein, Austria), where the term was formally introduced by Emil Zuckerkandl. In this time, Molecular Anthropology has developed both methodologically and theoretically and extended its applications, so covering key aspects of human evolution such as the reconstruction of the history of human populations and peopling processes, the characterization of DNA in extinct humans and the role of adaptive processes in shaping the genetic diversity of our species. In the current scientific panorama, molecular anthropologists have to face a double challenge. As members of the anthropological community, we are strongly committed to the integration of biological findings and other lines of evidence (e.g. linguistic and archaeological), while keeping in line with methodological innovations which are moving the ...

Molecular Phylogenetics and Evolution, 2008

Microbial pathogens, and viruses in particular, can serve as important complements to traditional... more Microbial pathogens, and viruses in particular, can serve as important complements to traditional genetic markers when investigating the population histories of their human host. The range of mutation rates for DNA viruses suggests that DNA viruses can be useful markers of both recent and ancient events in their host histories. Here, we assess the utility of a well known DNA virus, JC virus (JCV), for investigating human history and demography. Using complete coding viral genomes, we confirm the phylogeographic structure of JCV in populations worldwide and provide coalescent estimates of its evolutionary rate under two alternative models of its history. Using these rate estimates, we compare Bayesian skyline plots of population size changes for JCV to those of its human host as estimated with coding mitochondrial genomes of the latter. These comparisons, when combined with other evidence including a log Bayes Factor model test, show that JCV is evolving rapidly and is therefore tracking the recent history of its human host. These results support the hypothesis that post-World War II societal changes are most likely responsible for the recent demographic patterns observed among different regional JCV populations. In sum, fast evolving DNA viruses, such as JCV, can complement RNA viruses to provide novel insights about the recent history and demography of their human host.

Annual Review of Genomics and Human Genetics, 2004

Key Words genetic history, population structure, Mendelian and complex disease I Abstract Over th... more Key Words genetic history, population structure, Mendelian and complex disease I Abstract Over the past two decades, detailed studies of mitochondrial DNA and the Y chromosome have increased our understanding of the history and population genetics of Native American populations. Variation in autosomal DNA has also been investigated, but to a more limited extent. A low level of genetic diversity in Native American populations is a robust finding from all lines of evidence. In contrast to the previous multiple migration scenarios for the Pleistocene peopling of the Americas, it now seems that a single migration satisfactorily explains the genetic data. Native Americans show greater genetic similarity to populations in east central Asia than they do to the current easternmost Siberian populations. Recent studies on the Y chromosome indicate a date of entry (about 17,000 years ago) into the Americas roughly consistent with the archaeological record. Native Americans experienced two episodes of reduced population size: one with the peopling of the Americas and the other with European contact. The former is the more important determinant for the number of gene lineages and founding haplotypes seen in populations. It may also be an important determinant of the genetic variation underlying common complex diseases, and especially diabetes. The tribal structure of contemporary Native American populations is relevant to the distribution of rare Mendelian disorders because most tribes constitute relatively small, semi-independent gene pools. This leads us to expect that the allelic spectrum for Mendelian diseases will be simple within individual tribes but complex for Native Americans as a whole.

PLoS Genetics, 2014

Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In... more Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In the most recent genomic studies, this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years. However, mitochondrial and Y chromosome data are suggestive of earlier episodes of admixture. To investigate this further, we generated new genome-wide SNP data for a Yemeni population sample and merged these new data with published genome-wide genetic data from the HOA and a broad selection of surrounding populations. We used multidimensional scaling and ADMIXTURE methods in an exploratory data analysis to develop hypotheses on admixture and population structure in HOA populations. These analyses suggested that there might be distinct, differentiated African and non-African ancestries in the HOA. After partitioning the SNP data into African and non-African origin chromosome segments, we found support for a distinct African (Ethiopic) ancestry and a distinct non-African (Ethio-Somali) ancestry in HOA populations. The African Ethiopic ancestry is tightly restricted to HOA populations and likely represents an autochthonous HOA population. The non-African ancestry in the HOA, which is primarily attributed to a novel Ethio-Somali inferred ancestry component, is significantly differentiated from all neighboring non-African ancestries in North Africa, the Levant, and Arabia. The Ethio-Somali ancestry is found in all admixed HOA ethnic groups, shows little inter-individual variance within these ethnic groups, is estimated to have diverged from all other non-African ancestries by at least 23 ka, and does not carry the unique Arabian lactase persistence allele that arose about 4 ka. Taking into account published mitochondrial, Y chromosome, paleoclimate, and archaeological data, we find that the time of the Ethio-Somali back-to-Africa migration is most likely pre-agricultural.

American Journal of Tropical Medicine and Hygiene, 2014

American Journal of Tropical Medicine and Hygiene, 2015

Antimalarial drugs are a key tool in malaria elimination programs. With the emergence of artemisi... more Antimalarial drugs are a key tool in malaria elimination programs. With the emergence of artemisinin resistance in southeast Asia, an effort to identify molecular markers for surveillance of resistant malaria parasites is underway. Non-synonymous mutations in the kelch propeller domain (K13-propeller) in Plasmodium falciparum have been associated with artemisinin resistance in samples from southeast Asia, but additional studies are needed to characterize this locus in other P. falciparum populations with different levels of artemisinin use. Here, we sequenced the K13-propeller locus in 82 samples from Haiti, where limited government oversight of non-governmental organizations may have resulted in low-level use of artemisinin-based combination therapies. We detected a single-nucleotide polymorphism (SNP) at nucleotide 1,359 in a single isolate. Our results contribute to our understanding of the global genomic diversity of the K13-propeller locus in P. falciparum populations. Figure 1. A map of the study sites in Haiti. Most samples were collected from sites in the west (Ouest) and southeast (Sud-Est) departments represented by the blue diamonds. Smaller samples sets are represented by red stars. PJ, Dondorp AM, Day NP, White NJ, 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411-423.

The American journal of tropical medicine and hygiene, 2014

Sickle cell disease is a growing global health concern because infants born with the disorder in ... more Sickle cell disease is a growing global health concern because infants born with the disorder in developing countries are now surviving longer with little access to diagnostic and management options. In Haiti, the current state of sickle cell disease/trait in the population is unclear. To inform future screening efforts in Haiti, we assayed sickle hemoglobin mutations using traditional hemoglobin solubility tests (HST) and add-on techniques, which incorporated spectrophotometry and insoluble hemoglobin separation. We also generated genotype data as a metric for HST performance. We found 19 of 202 individuals screened with HST were positive for sickle hemoglobin, five of whom did not carry the HbS allele. We show that spectrophotometry and insoluble hemoglobin separation add-on techniques could resolve false positives associated with the traditional HST approach, with some limitations. We also discuss the incorporation of insoluble hemoglobin separation observation with HST in subopt...

Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the f... more Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the first successful global dispersal. This initial migration may have passed through Yemen, a region that has experienced multiple migrations events with Africa and Eurasia throughout human history. We use Bayesian phylogenetics to determine how ancient and recent migrations have shaped Yemeni mitogenomic variation. We sequenced 113 mitogenomes from multiple Yemeni regions with a focus on haplogroups M, N, and L3(xM,N) as these groups have the oldest evolutionary history outside of Africa. We performed Bayesian evolutionary analyses to generate time-measured phylogenies calibrated by Neanderthal and Denisovan mitogenomes in order to determine the age of Yemeni-specific clades. As defined by Yemeni monophyly, Yemeni in situ evolution is limited to the Holocene or latest Pleistocene (ages of clades in subhaplogroups L3b1a1a, L3h2, L3x1, M1a1f, M1a5, N1a1a3, and N1a3 range from 2 to 14 kya) and is often situated within broader Horn of Africa/southern Arabia in situ evolution (L3h2, L3x1, M1a1f, M1a5, and N1a1a3 ages range from 7 to 29 kya). Five subhaplogroups show no monophyly and are candidates for Holocene migration into Yemen (L0a2a2a, L3d1a1a, L3i2, M1a1b, and N1b1a). Yemeni mitogenomes are largely the product of Holocene migration, and subsequent in situ evolution, from Africa and western Eurasia. However, we hypothesize that recent population movements may obscure the genetic signature of more ancient migrations. Additional research, e.g., analyses of Yemeni nuclear genetic data, is needed to better reconstruct the complex population and migration histories associated with Out of Africa. Am J Phys Anthropol, 2015. © 2015 Wiley Periodicals, Inc.

PLoS ONE, 2013

Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia, is caused by the... more Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia, is caused by the expansion of the non-coding ATTCT pentanucleotide repeat in the ATAXIN 10 gene. To date, all cases of SCA10 are restricted to patients with ancestral ties to Latin American countries. Here, we report on a SCA10 patient with Sioux Native American ancestry and no reported Hispanic or Latino heritage. Neurological exam findings revealed impaired gait with mild, age-consistent cerebellar atrophy and no evidence of epileptic seizures. The age at onset for this patient, at 83 years of age, is the latest documented for SCA10 patients and is suggestive of a reduced penetrance allele in his family. Southern blot analysis showed an SCA10 expanded allele of 1400 repeats. Established SNPs surrounding the SCA10 locus showed a disease haplotype consistent with the previously described ''SCA10 haplotype''. This case suggests that the SCA10 expansion represents an early mutation event that possibly occurred during the initial peopling of the Americas.

Proceedings of the Royal Society B: Biological Sciences, 2011

Genetic data from extant donkeys (Equus asinus) have revealed two distinct mitochondrial DNA hapl... more Genetic data from extant donkeys (Equus asinus) have revealed two distinct mitochondrial DNA haplogroups, suggestive of two separate domestication events in northeast Africa about 5000 years ago. Without distinct phylogeographic structure in domestic donkey haplogroups and with little information on the genetic makeup of the ancestral African wild ass, however, it has been difficult to identify wild ancestors and geographical origins for the domestic mitochondrial clades. Our analysis of ancient archaeological and historic museum samples provides the first genetic information on the historic Nubian wild ass (Equus africanus africanus), Somali wild ass (Equus africanus somaliensis) and ancient donkey. The results demonstrate that the Nubian wild ass was an ancestor of the first donkey haplogroup. In contrast, the Somali wild ass has considerable mitochondrial divergence from the Nubian wild ass and domestic donkeys. These findings resolve the long-standing issue of the role of the Nubian wild ass in the domestication of the donkey, but raise new questions regarding the second ancestor for the donkey. Our results illustrate the complexity of animal domestication, and have conservation implications for critically endangered Nubian and Somali wild ass.

Proceedings of the Royal Society B: Biological Sciences, 2009

The evolution of languages provides a unique opportunity to study human population history. The o... more The evolution of languages provides a unique opportunity to study human population history. The origin of Semitic and the nature of dispersals by Semitic-speaking populations are of great importance to our understanding of the ancient history of the Middle East and Horn of Africa. Semitic populations are associated with the oldest written languages and urban civilizations in the region, which gave rise to some of the world's first major religious and literary traditions. In this study, we employ Bayesian computational phylogenetic techniques recently developed in evolutionary biology to analyse Semitic lexical data by modelling language evolution and explicitly testing alternative hypotheses of Semitic history. We implement a relaxed linguistic clock to date language divergences and use epigraphic evidence for the sampling dates of extinct Semitic languages to calibrate the rate of language evolution. Our statistical tests of alternative Semitic histories support an initial divergence of Akkadian from ancestral Semitic over competing hypotheses (e.g. an African origin of Semitic). We estimate an Early Bronze Age origin for Semitic approximately 5750 years ago in the Levant, and further propose that contemporary Ethiosemitic languages of Africa reflect a single introduction of early Ethiosemitic from southern Arabia approximately 2800 years ago.

PLoS ONE, 2009

Background: The role of race in human genetics and biomedical research is among the most conteste... more Background: The role of race in human genetics and biomedical research is among the most contested issues in science. Much debate centers on the relative importance of genetic versus sociocultural factors in explaining racial inequalities in health. However, few studies integrate genetic and sociocultural data to test competing explanations directly.

Marina S. Ascunce, Andrew Kitchen, Peter R. Schmidt, Michael M. Miyamoto, and Connie J. Mulligan ... more Marina S. Ascunce, Andrew Kitchen, Peter R. Schmidt, Michael M. Miyamoto, and Connie J. Mulligan (2006) An unusual pattern of ancient mitochondrial DNA haplogroups in northern African cattle. Zoological Studies 46(1): xxx-xxx. In

American Journal of Physical Anthropology

Southern Arabia and the Horn of Africa are important geographic centers for the study of human po... more Southern Arabia and the Horn of Africa are important geographic centers for the study of human population history because a great deal of migration has characterized these regions since the first emergence of humans out of Africa. Analysis of Jewish groups pro-vides a unique opportunity to investigate more recent population histories in this area. Mitochondrial DNA is used to investigate the maternal evolutionary history and can be combined with historical and linguistic data to test various population histories. In this study, we assay mitochondrial control region DNA sequence and diagnostic coding variants in Yemenite (n 5 45) and Ethiopian (n 5 41) Jewish populations, as well as in neighboring non-Jewish Yemeni (n 5 50) and Ethiopian (previously published Semitic speakers) populations. We investigate their population histories through a com-parison of haplogroup distributions and phylogenetic networks. A high frequency of sub-Saharan African L haplogroups was found in both Jewish...

Malaria journal, 2015

Haiti and the Dominican Republic, which share the island of Hispaniola, are the last locations in... more Haiti and the Dominican Republic, which share the island of Hispaniola, are the last locations in the Caribbean where malaria still persists. Malaria is an important public health concern in Haiti with 17,094 reported cases in 2014. Further, on January 12, 2010, a record earthquake devastated densely populated areas in Haiti including many healthcare and laboratory facilities. Weakened infrastructure provided fertile reservoirs for uncontrolled transmission of infectious pathogens. This situation results in unique challenges for malaria epidemiology and elimination efforts. To help Haiti achieve its malaria elimination goals by year 2020, the Laboratoire National de Santé Publique and Henry Ford Health System, in close collaboration with the Direction d'Épidémiologie, de Laboratoire et de Recherches and the Programme National de Contrôle de la Malaria, hosted a scientific meeting on "Elimination Strategies for Malaria in Haiti" on January 29-30, 2015 at the National La...

Methods in enzymology, 2005

The use of ancient DNA (aDNA) in the reconstruction of population origins and evolution is becomi... more The use of ancient DNA (aDNA) in the reconstruction of population origins and evolution is becoming increasingly common. Novel methods exist for the isolation, purification, and analysis of aDNA because these DNA templates are likely to be damaged, fragmented and?or associated with non-nucleic acid material. However, contamination of ancient specimens and DNA extracts with modern DNA is more widespread than is generally acknowledged and remains a significant problem in aDNA analysis. Studies of human aDNA are uniquely sensitive to contamination due to the continual presence of potential contamination sources. Meticulous authentication of results and careful selection of polymorphic markers capable of distinguishing between aDNA and probable DNA contaminants are critical to a successful aDNA study.

Journal of anthropological sciences = Rivista di antropologia : JASS / Istituto italiano di antropologia, 2010

Molecular Anthropology is a relatively young field of research. In fact, less than 50 years have ... more Molecular Anthropology is a relatively young field of research. In fact, less than 50 years have passed since the symposium "Classification and Human Evolution" (1962, Burg Wartenstein, Austria), where the term was formally introduced by Emil Zuckerkandl. In this time, Molecular Anthropology has developed both methodologically and theoretically and extended its applications, so covering key aspects of human evolution such as the reconstruction of the history of human populations and peopling processes, the characterization of DNA in extinct humans and the role of adaptive processes in shaping the genetic diversity of our species. In the current scientific panorama, molecular anthropologists have to face a double challenge. As members of the anthropological community, we are strongly committed to the integration of biological findings and other lines of evidence (e.g. linguistic and archaeological), while keeping in line with methodological innovations which are moving the ...

Molecular Phylogenetics and Evolution, 2008

Microbial pathogens, and viruses in particular, can serve as important complements to traditional... more Microbial pathogens, and viruses in particular, can serve as important complements to traditional genetic markers when investigating the population histories of their human host. The range of mutation rates for DNA viruses suggests that DNA viruses can be useful markers of both recent and ancient events in their host histories. Here, we assess the utility of a well known DNA virus, JC virus (JCV), for investigating human history and demography. Using complete coding viral genomes, we confirm the phylogeographic structure of JCV in populations worldwide and provide coalescent estimates of its evolutionary rate under two alternative models of its history. Using these rate estimates, we compare Bayesian skyline plots of population size changes for JCV to those of its human host as estimated with coding mitochondrial genomes of the latter. These comparisons, when combined with other evidence including a log Bayes Factor model test, show that JCV is evolving rapidly and is therefore tracking the recent history of its human host. These results support the hypothesis that post-World War II societal changes are most likely responsible for the recent demographic patterns observed among different regional JCV populations. In sum, fast evolving DNA viruses, such as JCV, can complement RNA viruses to provide novel insights about the recent history and demography of their human host.

Annual Review of Genomics and Human Genetics, 2004

Key Words genetic history, population structure, Mendelian and complex disease I Abstract Over th... more Key Words genetic history, population structure, Mendelian and complex disease I Abstract Over the past two decades, detailed studies of mitochondrial DNA and the Y chromosome have increased our understanding of the history and population genetics of Native American populations. Variation in autosomal DNA has also been investigated, but to a more limited extent. A low level of genetic diversity in Native American populations is a robust finding from all lines of evidence. In contrast to the previous multiple migration scenarios for the Pleistocene peopling of the Americas, it now seems that a single migration satisfactorily explains the genetic data. Native Americans show greater genetic similarity to populations in east central Asia than they do to the current easternmost Siberian populations. Recent studies on the Y chromosome indicate a date of entry (about 17,000 years ago) into the Americas roughly consistent with the archaeological record. Native Americans experienced two episodes of reduced population size: one with the peopling of the Americas and the other with European contact. The former is the more important determinant for the number of gene lineages and founding haplotypes seen in populations. It may also be an important determinant of the genetic variation underlying common complex diseases, and especially diabetes. The tribal structure of contemporary Native American populations is relevant to the distribution of rare Mendelian disorders because most tribes constitute relatively small, semi-independent gene pools. This leads us to expect that the allelic spectrum for Mendelian diseases will be simple within individual tribes but complex for Native Americans as a whole.

PLoS Genetics, 2014

Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In... more Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In the most recent genomic studies, this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years. However, mitochondrial and Y chromosome data are suggestive of earlier episodes of admixture. To investigate this further, we generated new genome-wide SNP data for a Yemeni population sample and merged these new data with published genome-wide genetic data from the HOA and a broad selection of surrounding populations. We used multidimensional scaling and ADMIXTURE methods in an exploratory data analysis to develop hypotheses on admixture and population structure in HOA populations. These analyses suggested that there might be distinct, differentiated African and non-African ancestries in the HOA. After partitioning the SNP data into African and non-African origin chromosome segments, we found support for a distinct African (Ethiopic) ancestry and a distinct non-African (Ethio-Somali) ancestry in HOA populations. The African Ethiopic ancestry is tightly restricted to HOA populations and likely represents an autochthonous HOA population. The non-African ancestry in the HOA, which is primarily attributed to a novel Ethio-Somali inferred ancestry component, is significantly differentiated from all neighboring non-African ancestries in North Africa, the Levant, and Arabia. The Ethio-Somali ancestry is found in all admixed HOA ethnic groups, shows little inter-individual variance within these ethnic groups, is estimated to have diverged from all other non-African ancestries by at least 23 ka, and does not carry the unique Arabian lactase persistence allele that arose about 4 ka. Taking into account published mitochondrial, Y chromosome, paleoclimate, and archaeological data, we find that the time of the Ethio-Somali back-to-Africa migration is most likely pre-agricultural.

American Journal of Tropical Medicine and Hygiene, 2014

American Journal of Tropical Medicine and Hygiene, 2015

Antimalarial drugs are a key tool in malaria elimination programs. With the emergence of artemisi... more Antimalarial drugs are a key tool in malaria elimination programs. With the emergence of artemisinin resistance in southeast Asia, an effort to identify molecular markers for surveillance of resistant malaria parasites is underway. Non-synonymous mutations in the kelch propeller domain (K13-propeller) in Plasmodium falciparum have been associated with artemisinin resistance in samples from southeast Asia, but additional studies are needed to characterize this locus in other P. falciparum populations with different levels of artemisinin use. Here, we sequenced the K13-propeller locus in 82 samples from Haiti, where limited government oversight of non-governmental organizations may have resulted in low-level use of artemisinin-based combination therapies. We detected a single-nucleotide polymorphism (SNP) at nucleotide 1,359 in a single isolate. Our results contribute to our understanding of the global genomic diversity of the K13-propeller locus in P. falciparum populations. Figure 1. A map of the study sites in Haiti. Most samples were collected from sites in the west (Ouest) and southeast (Sud-Est) departments represented by the blue diamonds. Smaller samples sets are represented by red stars. PJ, Dondorp AM, Day NP, White NJ, 2014. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371: 411-423.

The American journal of tropical medicine and hygiene, 2014

Sickle cell disease is a growing global health concern because infants born with the disorder in ... more Sickle cell disease is a growing global health concern because infants born with the disorder in developing countries are now surviving longer with little access to diagnostic and management options. In Haiti, the current state of sickle cell disease/trait in the population is unclear. To inform future screening efforts in Haiti, we assayed sickle hemoglobin mutations using traditional hemoglobin solubility tests (HST) and add-on techniques, which incorporated spectrophotometry and insoluble hemoglobin separation. We also generated genotype data as a metric for HST performance. We found 19 of 202 individuals screened with HST were positive for sickle hemoglobin, five of whom did not carry the HbS allele. We show that spectrophotometry and insoluble hemoglobin separation add-on techniques could resolve false positives associated with the traditional HST approach, with some limitations. We also discuss the incorporation of insoluble hemoglobin separation observation with HST in subopt...

Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the f... more Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the first successful global dispersal. This initial migration may have passed through Yemen, a region that has experienced multiple migrations events with Africa and Eurasia throughout human history. We use Bayesian phylogenetics to determine how ancient and recent migrations have shaped Yemeni mitogenomic variation. We sequenced 113 mitogenomes from multiple Yemeni regions with a focus on haplogroups M, N, and L3(xM,N) as these groups have the oldest evolutionary history outside of Africa. We performed Bayesian evolutionary analyses to generate time-measured phylogenies calibrated by Neanderthal and Denisovan mitogenomes in order to determine the age of Yemeni-specific clades. As defined by Yemeni monophyly, Yemeni in situ evolution is limited to the Holocene or latest Pleistocene (ages of clades in subhaplogroups L3b1a1a, L3h2, L3x1, M1a1f, M1a5, N1a1a3, and N1a3 range from 2 to 14 kya) and is often situated within broader Horn of Africa/southern Arabia in situ evolution (L3h2, L3x1, M1a1f, M1a5, and N1a1a3 ages range from 7 to 29 kya). Five subhaplogroups show no monophyly and are candidates for Holocene migration into Yemen (L0a2a2a, L3d1a1a, L3i2, M1a1b, and N1b1a). Yemeni mitogenomes are largely the product of Holocene migration, and subsequent in situ evolution, from Africa and western Eurasia. However, we hypothesize that recent population movements may obscure the genetic signature of more ancient migrations. Additional research, e.g., analyses of Yemeni nuclear genetic data, is needed to better reconstruct the complex population and migration histories associated with Out of Africa. Am J Phys Anthropol, 2015. © 2015 Wiley Periodicals, Inc.

PLoS ONE, 2013

Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia, is caused by the... more Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant cerebellar ataxia, is caused by the expansion of the non-coding ATTCT pentanucleotide repeat in the ATAXIN 10 gene. To date, all cases of SCA10 are restricted to patients with ancestral ties to Latin American countries. Here, we report on a SCA10 patient with Sioux Native American ancestry and no reported Hispanic or Latino heritage. Neurological exam findings revealed impaired gait with mild, age-consistent cerebellar atrophy and no evidence of epileptic seizures. The age at onset for this patient, at 83 years of age, is the latest documented for SCA10 patients and is suggestive of a reduced penetrance allele in his family. Southern blot analysis showed an SCA10 expanded allele of 1400 repeats. Established SNPs surrounding the SCA10 locus showed a disease haplotype consistent with the previously described ''SCA10 haplotype''. This case suggests that the SCA10 expansion represents an early mutation event that possibly occurred during the initial peopling of the Americas.

Proceedings of the Royal Society B: Biological Sciences, 2011

Genetic data from extant donkeys (Equus asinus) have revealed two distinct mitochondrial DNA hapl... more Genetic data from extant donkeys (Equus asinus) have revealed two distinct mitochondrial DNA haplogroups, suggestive of two separate domestication events in northeast Africa about 5000 years ago. Without distinct phylogeographic structure in domestic donkey haplogroups and with little information on the genetic makeup of the ancestral African wild ass, however, it has been difficult to identify wild ancestors and geographical origins for the domestic mitochondrial clades. Our analysis of ancient archaeological and historic museum samples provides the first genetic information on the historic Nubian wild ass (Equus africanus africanus), Somali wild ass (Equus africanus somaliensis) and ancient donkey. The results demonstrate that the Nubian wild ass was an ancestor of the first donkey haplogroup. In contrast, the Somali wild ass has considerable mitochondrial divergence from the Nubian wild ass and domestic donkeys. These findings resolve the long-standing issue of the role of the Nubian wild ass in the domestication of the donkey, but raise new questions regarding the second ancestor for the donkey. Our results illustrate the complexity of animal domestication, and have conservation implications for critically endangered Nubian and Somali wild ass.

Proceedings of the Royal Society B: Biological Sciences, 2009

The evolution of languages provides a unique opportunity to study human population history. The o... more The evolution of languages provides a unique opportunity to study human population history. The origin of Semitic and the nature of dispersals by Semitic-speaking populations are of great importance to our understanding of the ancient history of the Middle East and Horn of Africa. Semitic populations are associated with the oldest written languages and urban civilizations in the region, which gave rise to some of the world's first major religious and literary traditions. In this study, we employ Bayesian computational phylogenetic techniques recently developed in evolutionary biology to analyse Semitic lexical data by modelling language evolution and explicitly testing alternative hypotheses of Semitic history. We implement a relaxed linguistic clock to date language divergences and use epigraphic evidence for the sampling dates of extinct Semitic languages to calibrate the rate of language evolution. Our statistical tests of alternative Semitic histories support an initial divergence of Akkadian from ancestral Semitic over competing hypotheses (e.g. an African origin of Semitic). We estimate an Early Bronze Age origin for Semitic approximately 5750 years ago in the Levant, and further propose that contemporary Ethiosemitic languages of Africa reflect a single introduction of early Ethiosemitic from southern Arabia approximately 2800 years ago.

PLoS ONE, 2009

Background: The role of race in human genetics and biomedical research is among the most conteste... more Background: The role of race in human genetics and biomedical research is among the most contested issues in science. Much debate centers on the relative importance of genetic versus sociocultural factors in explaining racial inequalities in health. However, few studies integrate genetic and sociocultural data to test competing explanations directly.

American Journal of Physical Anthropology, Jan 1, 2008

Despite its key location for population movements out of and back into Africa, Yemen has not yet ... more Despite its key location for population movements out of and back into Africa, Yemen has not yet been sampled on a regional level for an investigation of sub-Saharan, West Eurasian, and South Asian genetic contributions. In this study, we present mitochondrial DNA (mtDNA) data for regionally distinct Yemeni populations that reveal different distributions of mtDNA lineages. An extensive database of mtDNA sequences from North and East African, Middle Eastern and Indian populations was analyzed to provide a context for the regional Yemeni mtDNA datasets. The groups of western Yemen appear to be most closely related to Middle Eastern and North African populations, while the eastern Yemeni population from Hadramawt is most closely related to East Africa. Furthermore, haplotype matches with Africa are almost exclusively confined to West Eurasian R0a haplogroup in southwestern Yemen, although more sub-Saharan L-type matches appear in more northern Yemeni populations. In fact, Yemeni populations have the highest frequency of R0a haplotypes detected to date, thus Yemen or southern Arabia may be the site of the initial expansion of this haplogroup. Whereas two variants of the sub-Saharan haplogroup M1 were detected only in southwestern Yemen close to the Bab el-Mandeb Strait, different non-African M haplotypes were detected at low frequencies (∼2%) in western parts of the country and at a higher frequency (7.5%) in the Hadramawt. We conclude that the Yemeni gene pool is highly stratified both regionally and temporally and that it has received West Eurasian, Northeast African, and South Asian gene flow. Am J Phys Anthropol, 2008. © 2008 Wiley-Liss, Inc.