Emily Lyons - Academia.edu (original) (raw)
Papers by Emily Lyons
Biology Letters, 2009
Studies of animal populations suggest that low genetic heterozygosity is an important risk factor... more Studies of animal populations suggest that low genetic heterozygosity is an important risk factor for infection by a diverse range of pathogens, but relatively little research has looked to see whether similar patterns exist in humans. We have used microsatellite genome screen data for tuberculosis (TB), hepatitis and leprosy to test the hypothesis that inbreeding depression increases risk of infection. Our results indicate that inbred individuals are more common among our infected cases for TB and hepatitis, but only in populations where consanguineous marriages are common. No effect was found either for leprosy, which is thought to be oligogenic, or for hepatitis in Italy where consanguineous marriages are rare. Our results suggest that consanguinity is an important risk factor in susceptibility to infectious diseases in humans.
Genome Biology
All members of the species Plasmodium falciparum seem to have been derived from a single recent a... more All members of the species Plasmodium falciparum seem to have been derived from a single recent ancestor. Significance and context The protozoan parasite Plasmodium falciparum causes malaria in humans. Its transmission and pathogenesis benefit from its genetic variation, which seriously affects attempts to combat this potentially deadly disease. An interesting feature of the malaria parasite is that DNA variation at silentthat is synonymous-sites in the coding sequences is very low, because of constraints in codon usage, whereas genetic variation in the proteins that act as antigenic determinants, or are involved in drug resistance or pathogenesis, is fairly large. On the other hand, microsatellite variation exists within and among subpopulations of P. falciparum. To investigate this genetic variation, the authors addressed the question of whether all extant P. falciparum cells have been derived from a single progenitor that spread through the human population by analyzing the intronic sequences of various P. falciparum genes. Introns are among the most rapidly evolving sequences in eukaryotes and are often used in studies of population structure.
Nature, Jan 6, 1997
Nature is the international weekly journal of science: a magazine style journal that publishes fu... more Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and ...
Trends in Parasitology, 2004
... Philadelphia, USA. Funding for the workshop was provided by The Ellison Medical Foundation, B... more ... Philadelphia, USA. Funding for the workshop was provided by The Ellison Medical Foundation, Burroughs Wellcome Fund, National Institute of Allergy and Infectious Diseases (NIAID) and The Institute for Genomic Research (TIGR). A ...
Trends in Parasitology, 2003
To date, coalescent analysis of the Plasmodium falciparum genome sequence has failed to provide a... more To date, coalescent analysis of the Plasmodium falciparum genome sequence has failed to provide a unifying theory regarding the parasite's evolution. While a better understanding of the evolution of the malaria genome will undoubtedly clarify the current controversy, the importance of the parasite's interplay with both the human host and mosquito vector cannot be underestimated. Changes in the population biology or ecology of either one of these species have consequences for malaria transmission and this was never more apparent than in the environmental changes brought about by the advent of agriculture.
Science, 2001
Genetic variability of Plasmodium falciparum underlies its transmission success and thwarts effor... more Genetic variability of Plasmodium falciparum underlies its transmission success and thwarts efforts to control disease caused by this parasite. Genetic variation in antigenic, drug resistance, and pathogenesis determinants is abundant, consistent with an ancient origin of P. falciparum, whereas DNA variation at silent (synonymous) sites in coding sequences appears virtually absent, consistent with a recent origin of the parasite. To resolve this paradox, we analyzed introns and demonstrated that these are deficient in single-nucleotide polymorphisms, as are synonymous sites in coding regions. These data establish the recent origin of P. falciparum and further provide an explanation for the abundant diversity observed in antigen and other selected genes. Plasmodium falciparum causes the most virulent form of human malaria, resulting in 200 million to 300 million infections and 1 million to 3 million deaths annually (1). Genetic variation within this human pathogen facilitates its transmission and pathogenesis and limits efforts to combat the disease. In the case of P. falciparum, the issue is caught up in controversy (2, 3). Genetic variation in proteins for antigenic determinants (4), drug resistance (5-8), and pathogenesis is abundant (9-13), whereas DNA variation at silent (synonymous) sites in coding sequences appears virtually absent (14). Nevertheless, microsatellite variation within and among subpopulations is widespread (15, 16). These discrepancies could be reconciled if all extant P. falciparum derived from a single progenitor that spread through the human population within the past few thousand years (14). Alternatively, codon usage may be so constrained that synonymous mutations are eliminated by selection. To resolve these possibilities, we analyzed 25 introns from eight independent isolates and found only eight single-nucleotide polymorphisms (SNPs), five of which occur within microsatellite repeats. In contrast, microsatellite polymor
Nature Genetics, 2007
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MH... more We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
The Journal of Infectious Diseases, 2009
Introduction. Light microscopy examination of blood slides is the main method of detecting malari... more Introduction. Light microscopy examination of blood slides is the main method of detecting malaria infection; however, it has limited sensitivity. Low-density infections are most likely to be missed, but they contribute to the infectious reservoir. Quantifying these submicroscopic infections is therefore key to understanding transmission dynamics and successfully reducing parasite transmission. Methods. We conducted a systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique. The combined microscopy:PCR prevalence ratio was estimated by random-effects meta-analysis, and the effect of covariates was determined by meta-regression. Results. Seventy-two pairs of prevalence measurements were included in the study. The prevalence of infection measured by microscopy was, on average, 50.8% (95% confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte-specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%-26.6%) of the prevalence measured by PCR. A significantly higher percentage of total infections was detected by microscopy in areas of high, compared with low, transmission (74.5% when the prevalence determined by PCR was 175% versus 12.0% when the prevalence determined by PCR was !10%). Discussion. Microscopy can miss a substantial proportion of P. falciparum infections in surveys of endemic populations, especially in areas with low transmission of infection. The extent of the submicroscopic reservoir needs to be taken into account for effective surveillance and control.
Infection, Genetics and Evolution, 2002
Evolution, 1998
Synergism among mutations can lead to an advantage to sexual reproduction, provided mutation rate... more Synergism among mutations can lead to an advantage to sexual reproduction, provided mutation rates are high enough (the mutational deterministic hypothesis). Here we tested the idea that competition for food can increase the advantage to sexual reproduction, perhaps by increasing the synergism among mutations in asexual individuals. We compared the survivorship of sexual and asexual snails (Potamopyrgus antipodarum) under two treatments: starved and fed. We predicted higher mortality for asexual snails when starved, but found that sexual and asexual individuals survived at the same rate, independent of treatment. These results suggest that the distribution of sex in this snail may not be explained by variation in competition among populations.
ABSTRACT Thesis (M.S.)--Michigan State University. Dept. of Botany and Plant Pathology, 1996. Inc... more ABSTRACT Thesis (M.S.)--Michigan State University. Dept. of Botany and Plant Pathology, 1996. Includes bibliographical references (leaves 48-51).
Introduction. Light microscopy examination of blood slides is the main method of detecting malari... more Introduction. Light microscopy examination of blood slides is the main method of detecting malaria infection; however, it has limited sensitivity. Low-density infections are most likely to be missed, but they contribute to the infectious reservoir. Quantifying these submicroscopic infections is therefore key to understanding transmission dynamics and successfully reducing parasite transmission. Methods. We conducted a systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique. The combined microscopy:PCR prevalence ratio was estimated by random-effects meta-analysis, and the effect of covariates was determined by meta-regression. Results. Seventy-two pairs of prevalence measurements were included in the study. The prevalence of infection measured by microscopy was, on average, 50.8% (95% confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte-specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%-26.6%) of the prevalence measured by PCR. A significantly higher percentage of total infections was detected by microscopy in areas of high, compared with low, transmission (74.5% when the prevalence determined by PCR was 175% versus 12.0% when the prevalence determined by PCR was !10%). Discussion. Microscopy can miss a substantial proportion of P. falciparum infections in surveys of endemic populations, especially in areas with low transmission of infection. The extent of the submicroscopic reservoir needs to be taken into account for effective surveillance and control.
Introduction. Light microscopy examination of blood slides is the main method of detecting malari... more Introduction. Light microscopy examination of blood slides is the main method of detecting malaria infection; however, it has limited sensitivity. Low-density infections are most likely to be missed, but they contribute to the infectious reservoir. Quantifying these submicroscopic infections is therefore key to understanding transmission dynamics and successfully reducing parasite transmission. Methods. We conducted a systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique. The combined microscopy:PCR prevalence ratio was estimated by random-effects meta-analysis, and the effect of covariates was determined by meta-regression. Results. Seventy-two pairs of prevalence measurements were included in the study. The prevalence of infection measured by microscopy was, on average, 50.8% (95% confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte-specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%-26.6%) of the prevalence measured by PCR. A significantly higher percentage of total infections was detected by microscopy in areas of high, compared with low, transmission (74.5% when the prevalence determined by PCR was 175% versus 12.0% when the prevalence determined by PCR was !10%). Discussion. Microscopy can miss a substantial proportion of P. falciparum infections in surveys of endemic populations, especially in areas with low transmission of infection. The extent of the submicroscopic reservoir needs to be taken into account for effective surveillance and control.
Biology Letters, 2009
Studies of animal populations suggest thatl ow genetich eterozygosityi sa ni mportant risk factor... more Studies of animal populations suggest thatl ow genetich eterozygosityi sa ni mportant risk factor for infectionb yadiverse range of pathogens, but relatively little research has lookedt o see whether similar patterns existi nh umans. We haveu sed microsatellite genome screen data for tuberculosis (TB), hepatitis and leprosy to test the hypothesis that inbreeding depression increasesr isk of infection. Ourr esults indicate that inbred individualsare more common among ouri nfectedc ases forT Ba nd hepatitis, buto nly in populationsw here consanguineous marriages arec ommon. No effect wasf ound either for leprosy, whichi st hought to be oligogenic,o rf or hepatitisinItaly whereconsanguineousmarriages arer are. Ourr esults suggest thatc onsanguinity is an importantr iskf actori ns usceptibilityt o infectiousdiseasesinhumans.
Biology Letters, 2009
Studies of animal populations suggest that low genetic heterozygosity is an important risk factor... more Studies of animal populations suggest that low genetic heterozygosity is an important risk factor for infection by a diverse range of pathogens, but relatively little research has looked to see whether similar patterns exist in humans. We have used microsatellite genome screen data for tuberculosis (TB), hepatitis and leprosy to test the hypothesis that inbreeding depression increases risk of infection. Our results indicate that inbred individuals are more common among our infected cases for TB and hepatitis, but only in populations where consanguineous marriages are common. No effect was found either for leprosy, which is thought to be oligogenic, or for hepatitis in Italy where consanguineous marriages are rare. Our results suggest that consanguinity is an important risk factor in susceptibility to infectious diseases in humans.
Genome Biology
All members of the species Plasmodium falciparum seem to have been derived from a single recent a... more All members of the species Plasmodium falciparum seem to have been derived from a single recent ancestor. Significance and context The protozoan parasite Plasmodium falciparum causes malaria in humans. Its transmission and pathogenesis benefit from its genetic variation, which seriously affects attempts to combat this potentially deadly disease. An interesting feature of the malaria parasite is that DNA variation at silentthat is synonymous-sites in the coding sequences is very low, because of constraints in codon usage, whereas genetic variation in the proteins that act as antigenic determinants, or are involved in drug resistance or pathogenesis, is fairly large. On the other hand, microsatellite variation exists within and among subpopulations of P. falciparum. To investigate this genetic variation, the authors addressed the question of whether all extant P. falciparum cells have been derived from a single progenitor that spread through the human population by analyzing the intronic sequences of various P. falciparum genes. Introns are among the most rapidly evolving sequences in eukaryotes and are often used in studies of population structure.
Nature, Jan 6, 1997
Nature is the international weekly journal of science: a magazine style journal that publishes fu... more Nature is the international weekly journal of science: a magazine style journal that publishes full-length research papers in all disciplines of science, as well as News and Views, reviews, news, features, commentaries, web focuses and more, covering all branches of science and ...
Trends in Parasitology, 2004
... Philadelphia, USA. Funding for the workshop was provided by The Ellison Medical Foundation, B... more ... Philadelphia, USA. Funding for the workshop was provided by The Ellison Medical Foundation, Burroughs Wellcome Fund, National Institute of Allergy and Infectious Diseases (NIAID) and The Institute for Genomic Research (TIGR). A ...
Trends in Parasitology, 2003
To date, coalescent analysis of the Plasmodium falciparum genome sequence has failed to provide a... more To date, coalescent analysis of the Plasmodium falciparum genome sequence has failed to provide a unifying theory regarding the parasite's evolution. While a better understanding of the evolution of the malaria genome will undoubtedly clarify the current controversy, the importance of the parasite's interplay with both the human host and mosquito vector cannot be underestimated. Changes in the population biology or ecology of either one of these species have consequences for malaria transmission and this was never more apparent than in the environmental changes brought about by the advent of agriculture.
Science, 2001
Genetic variability of Plasmodium falciparum underlies its transmission success and thwarts effor... more Genetic variability of Plasmodium falciparum underlies its transmission success and thwarts efforts to control disease caused by this parasite. Genetic variation in antigenic, drug resistance, and pathogenesis determinants is abundant, consistent with an ancient origin of P. falciparum, whereas DNA variation at silent (synonymous) sites in coding sequences appears virtually absent, consistent with a recent origin of the parasite. To resolve this paradox, we analyzed introns and demonstrated that these are deficient in single-nucleotide polymorphisms, as are synonymous sites in coding regions. These data establish the recent origin of P. falciparum and further provide an explanation for the abundant diversity observed in antigen and other selected genes. Plasmodium falciparum causes the most virulent form of human malaria, resulting in 200 million to 300 million infections and 1 million to 3 million deaths annually (1). Genetic variation within this human pathogen facilitates its transmission and pathogenesis and limits efforts to combat the disease. In the case of P. falciparum, the issue is caught up in controversy (2, 3). Genetic variation in proteins for antigenic determinants (4), drug resistance (5-8), and pathogenesis is abundant (9-13), whereas DNA variation at silent (synonymous) sites in coding sequences appears virtually absent (14). Nevertheless, microsatellite variation within and among subpopulations is widespread (15, 16). These discrepancies could be reconciled if all extant P. falciparum derived from a single progenitor that spread through the human population within the past few thousand years (14). Alternatively, codon usage may be so constrained that synonymous mutations are eliminated by selection. To resolve these possibilities, we analyzed 25 introns from eight independent isolates and found only eight single-nucleotide polymorphisms (SNPs), five of which occur within microsatellite repeats. In contrast, microsatellite polymor
Nature Genetics, 2007
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MH... more We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
The Journal of Infectious Diseases, 2009
Introduction. Light microscopy examination of blood slides is the main method of detecting malari... more Introduction. Light microscopy examination of blood slides is the main method of detecting malaria infection; however, it has limited sensitivity. Low-density infections are most likely to be missed, but they contribute to the infectious reservoir. Quantifying these submicroscopic infections is therefore key to understanding transmission dynamics and successfully reducing parasite transmission. Methods. We conducted a systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique. The combined microscopy:PCR prevalence ratio was estimated by random-effects meta-analysis, and the effect of covariates was determined by meta-regression. Results. Seventy-two pairs of prevalence measurements were included in the study. The prevalence of infection measured by microscopy was, on average, 50.8% (95% confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte-specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%-26.6%) of the prevalence measured by PCR. A significantly higher percentage of total infections was detected by microscopy in areas of high, compared with low, transmission (74.5% when the prevalence determined by PCR was 175% versus 12.0% when the prevalence determined by PCR was !10%). Discussion. Microscopy can miss a substantial proportion of P. falciparum infections in surveys of endemic populations, especially in areas with low transmission of infection. The extent of the submicroscopic reservoir needs to be taken into account for effective surveillance and control.
Infection, Genetics and Evolution, 2002
Evolution, 1998
Synergism among mutations can lead to an advantage to sexual reproduction, provided mutation rate... more Synergism among mutations can lead to an advantage to sexual reproduction, provided mutation rates are high enough (the mutational deterministic hypothesis). Here we tested the idea that competition for food can increase the advantage to sexual reproduction, perhaps by increasing the synergism among mutations in asexual individuals. We compared the survivorship of sexual and asexual snails (Potamopyrgus antipodarum) under two treatments: starved and fed. We predicted higher mortality for asexual snails when starved, but found that sexual and asexual individuals survived at the same rate, independent of treatment. These results suggest that the distribution of sex in this snail may not be explained by variation in competition among populations.
ABSTRACT Thesis (M.S.)--Michigan State University. Dept. of Botany and Plant Pathology, 1996. Inc... more ABSTRACT Thesis (M.S.)--Michigan State University. Dept. of Botany and Plant Pathology, 1996. Includes bibliographical references (leaves 48-51).
Introduction. Light microscopy examination of blood slides is the main method of detecting malari... more Introduction. Light microscopy examination of blood slides is the main method of detecting malaria infection; however, it has limited sensitivity. Low-density infections are most likely to be missed, but they contribute to the infectious reservoir. Quantifying these submicroscopic infections is therefore key to understanding transmission dynamics and successfully reducing parasite transmission. Methods. We conducted a systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique. The combined microscopy:PCR prevalence ratio was estimated by random-effects meta-analysis, and the effect of covariates was determined by meta-regression. Results. Seventy-two pairs of prevalence measurements were included in the study. The prevalence of infection measured by microscopy was, on average, 50.8% (95% confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte-specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%-26.6%) of the prevalence measured by PCR. A significantly higher percentage of total infections was detected by microscopy in areas of high, compared with low, transmission (74.5% when the prevalence determined by PCR was 175% versus 12.0% when the prevalence determined by PCR was !10%). Discussion. Microscopy can miss a substantial proportion of P. falciparum infections in surveys of endemic populations, especially in areas with low transmission of infection. The extent of the submicroscopic reservoir needs to be taken into account for effective surveillance and control.
Introduction. Light microscopy examination of blood slides is the main method of detecting malari... more Introduction. Light microscopy examination of blood slides is the main method of detecting malaria infection; however, it has limited sensitivity. Low-density infections are most likely to be missed, but they contribute to the infectious reservoir. Quantifying these submicroscopic infections is therefore key to understanding transmission dynamics and successfully reducing parasite transmission. Methods. We conducted a systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique. The combined microscopy:PCR prevalence ratio was estimated by random-effects meta-analysis, and the effect of covariates was determined by meta-regression. Results. Seventy-two pairs of prevalence measurements were included in the study. The prevalence of infection measured by microscopy was, on average, 50.8% (95% confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte-specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%-26.6%) of the prevalence measured by PCR. A significantly higher percentage of total infections was detected by microscopy in areas of high, compared with low, transmission (74.5% when the prevalence determined by PCR was 175% versus 12.0% when the prevalence determined by PCR was !10%). Discussion. Microscopy can miss a substantial proportion of P. falciparum infections in surveys of endemic populations, especially in areas with low transmission of infection. The extent of the submicroscopic reservoir needs to be taken into account for effective surveillance and control.
Biology Letters, 2009
Studies of animal populations suggest thatl ow genetich eterozygosityi sa ni mportant risk factor... more Studies of animal populations suggest thatl ow genetich eterozygosityi sa ni mportant risk factor for infectionb yadiverse range of pathogens, but relatively little research has lookedt o see whether similar patterns existi nh umans. We haveu sed microsatellite genome screen data for tuberculosis (TB), hepatitis and leprosy to test the hypothesis that inbreeding depression increasesr isk of infection. Ourr esults indicate that inbred individualsare more common among ouri nfectedc ases forT Ba nd hepatitis, buto nly in populationsw here consanguineous marriages arec ommon. No effect wasf ound either for leprosy, whichi st hought to be oligogenic,o rf or hepatitisinItaly whereconsanguineousmarriages arer are. Ourr esults suggest thatc onsanguinity is an importantr iskf actori ns usceptibilityt o infectiousdiseasesinhumans.