M J Mosher | Western Washington University (original) (raw)

Papers by M J Mosher

The International Encyclopedia of Biological Anthropology, 2018

Diabetes, 2021

Type 2 DM in patients with BMIs > 25 is well defined. Gaps exist in understanding lean diabete... more Type 2 DM in patients with BMIs > 25 is well defined. Gaps exist in understanding lean diabetes (LD), those with BMI < 25. In the US, LD presents in < 12% of patients and most prevalent in minorities. Childhood malnutrition, low socioeconomic status, and early age of onset contribute to this disease variant in developing countries. In Peru, diabetes is estimated to be prevalent in 7% of the population and may be, contrary to some publications, more widespread in remote Amazonian communities where poverty is common and access to health care is lacking. This study identifies characteristics in LD in comparison to individuals with overweight/obese (OOD) type 2 diabetes in Peru. A subsample of individuals with diabetes from a larger pilot study were profiled [F/M = 42/24, age ≥ 18 yrs] in the Amazonian town of Yurimaguas, Peru. We collected glycated hemoglobin (HbA1c), fasting blood lipids panels, height and weight from participants. Diabetes was determined using American Diabe...

Human Biology, 2016

DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects r... more DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process. Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative functions include regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism, and reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examined the significance of variation in DNA methylation patterns along the leptin core promoter in four populations (phase 1) and used biomarkers reflecting leptin's functional process in two of those populations, western Buryat of Siberia and the Mennonite of central Kansas, to investigate the relevance of the ethnic variation identified in the DNA methylation (phase 2). LEP's core promoter region contains both the binding site for C/EBPα (CCAAT/enhancer binding protein alpha), which tempers the final step in adipocyte maturity and capacity to synthesize leptin, and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, suggesting tissue-specific methylation variation at this region (Melzner et al. 2002). We hypothesized that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers that reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system, and anthropometric measures.

Plos One, 2007

Background. The role of circulating levels of total homocysteine tHcy in the development of coron... more Background. The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD) is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met) in the Catechol-O-methyltransferase (COMT) gene. Methodology and Findings. Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middleaged men from eastern Finland. A population-based prospective cohort of 792 men aged 46-64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR) of 1.73 (95% confidence interval (CI), 1.07-2.79), and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05-2.77). Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93-2.49), subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50-5.76) as compared with other men. Conclusions. This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels.

Human Biology, 2005

Low levels of high-density lipoprotein (HDL) are widely documented as a risk factor for cardiovas... more Low levels of high-density lipoprotein (HDL) are widely documented as a risk factor for cardiovascular disease (CVD). Furthermore, there

Human Biology, 2005

Pooled DNA samples have been used in association studies of Mendelian disease genes. This method ... more Pooled DNA samples have been used in association studies of Mendelian disease genes. This method involves combining equal quantities of DNA from patients and control subjects into separate pools and comparing the pools for distributions of genetic markers. In this study identical quantities of DNA from 300 individuals representing 6 populations were pooled and amplified for 296 loci using the touchdown polymerase chain reaction (PCR) method. The purpose of this study is to test the efficacy of pooled DNA markers in the reconstruction of the genetic structure of human populations. The populations sampled included Chuvash, Buryats, Kizhi, Native Americans, South Africans, and New York City whites. To test the accuracy of the allele-frequency distributions, we genotyped the Buryats and New York samples individually for six microsatellite markers and compared their frequencies to the allele frequencies derived from the electropherogram peak heights for the pooled DNA, producing a correlation of 0.9811 with a variance of less than 0.04. Two-dimensional scaling of genetic distances among the six populations produced clusters that reflected known historical relationships. A distance matrix was created using all 296 loci, and matrices based on individual chromosomes were correlated against the total matrix. As expected, the largest chromosomes had the highest correlations with the total matrix, whereas one of the smallest chromosomes, chromosome 22, had the lowest correlation and differed most from the combined STR distance matrix. Genetic markers and their allele frequencies in human populations reflect the evolutionary history and the genetic structure of these aggregates. However,

Human Biology, 2010

We examined mitochondrial DNA (mtDNA) variation in six Mennonite communities from Kansas (Goessel... more We examined mitochondrial DNA (mtDNA) variation in six Mennonite communities from Kansas (Goessel, Lone Tree, Garden View, Meridian, and Garden City) and Nebraska (Henderson) to determine their genetic structure and its relationship to population history. Mitochondrial DNA haplogroup and haplotype information were obtained from blood samples from 118 individuals. Molecular genetic variation was analyzed using diversity measures, neutrality test statistics, spatial analysis of molecular variance (SAMOVA), and multidimensional scaling plots. The Mennonite samples exhibited eight western European mtDNA haplogroups: H, HV0, I, J, K, T, U, and X. Comparable to other populations of European descent, haplogroup H was the most frequent in all six communities and ranged from 35% in Lone Tree to 75% in Old Order Mennonites from Garden City. Fifty-eight different mtDNA haplotypes were found in these groups with only one shared among all six populations. Haplotype diversities varied from 0.81 in Goessel to 0.96 in Henderson and Garden View. Multivariate statistical analysis of these populations indicates that these Anabaptist communities formed new congregations by fissioning along familial lines. Population subdivision of these communities into congregations supports previously documented patterns of fission-fusion. These haploid molecular data provide a more accurate reflection of biological relationships between midwestern Mennonite communities than evidence based on classical genetic markers.

Journal of Archaeological Science: Reports, 2016

Epigenetic mechanisms have been widely studied for the past several decades, yet despite a surfei... more Epigenetic mechanisms have been widely studied for the past several decades, yet despite a surfeit of literature examining animal models and extensive human research associating these mechanisms with pathology, little is known regarding the normal variation among populations or the phenotypic relevance of that variation. Moreover, no one is certain of the evolutionary significance these mechanisms and their underlying machinery. Their structure and function are highly dependent upon dietary intake of indispensable nutrients, yet nutrient profiles vary across populations and generations in an ongoing manner and energy intake can fluctuate dramatically. Here, we examine how the DNA methylation might archive ancestral dietary patterns and discuss the initial findings in a pilot study on population variation in DNA methylation patterns in four maternal/offspring duos from three continents (n = 88). This pilot examined DNA methylation patterns across the core promoter of the metabolic gene leptin (LEP), a leading regulator of energy homeostasis and adipogenesis. Remarkably similar overall mean patterns were present across 7 CpG sites which include the C/EBPα transcription binding site, and two sites proximal to the TATA. Findings suggest a stable and conserved DNA methylation pattern in this region of the (LEP) promoter across populations consuming diets from varying food chains.

abstract DNA methylation is the most widely studied of epigenetic mechanisms, with environmental ... more abstract DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process. Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative functions include regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism, and reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examined the significance of variation in DNA methylation patterns along the leptin core promoter in four populations (phase 1) and used biomarkers reflecting leptin's functional process in two of those populations, western Buryat of Siberia and the Mennonite of central Kansas, to investigate the relevance of the ethnic variation identified in the DNA methylation (phase 2). LEP's core promoter region contains both the binding site for C/EBPα (CCAAT/enhancer binding protein alpha), which tempers the final step in adipocyte maturity and capacity to synthesize leptin, and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, suggesting tissue-specific methylation variation at this region (Melzner et al. 2002). We hypothesized that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers that reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system, and anthropometric measures.

An Evolutionary Perspective, 2000

The International Encyclopedia of Biological Anthropology, 2018

Diabetes, 2021

Type 2 DM in patients with BMIs > 25 is well defined. Gaps exist in understanding lean diabete... more Type 2 DM in patients with BMIs > 25 is well defined. Gaps exist in understanding lean diabetes (LD), those with BMI < 25. In the US, LD presents in < 12% of patients and most prevalent in minorities. Childhood malnutrition, low socioeconomic status, and early age of onset contribute to this disease variant in developing countries. In Peru, diabetes is estimated to be prevalent in 7% of the population and may be, contrary to some publications, more widespread in remote Amazonian communities where poverty is common and access to health care is lacking. This study identifies characteristics in LD in comparison to individuals with overweight/obese (OOD) type 2 diabetes in Peru. A subsample of individuals with diabetes from a larger pilot study were profiled [F/M = 42/24, age ≥ 18 yrs] in the Amazonian town of Yurimaguas, Peru. We collected glycated hemoglobin (HbA1c), fasting blood lipids panels, height and weight from participants. Diabetes was determined using American Diabe...

Human Biology, 2016

DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects r... more DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process. Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative functions include regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism, and reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examined the significance of variation in DNA methylation patterns along the leptin core promoter in four populations (phase 1) and used biomarkers reflecting leptin's functional process in two of those populations, western Buryat of Siberia and the Mennonite of central Kansas, to investigate the relevance of the ethnic variation identified in the DNA methylation (phase 2). LEP's core promoter region contains both the binding site for C/EBPα (CCAAT/enhancer binding protein alpha), which tempers the final step in adipocyte maturity and capacity to synthesize leptin, and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, suggesting tissue-specific methylation variation at this region (Melzner et al. 2002). We hypothesized that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers that reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system, and anthropometric measures.

Plos One, 2007

Background. The role of circulating levels of total homocysteine tHcy in the development of coron... more Background. The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD) is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met) in the Catechol-O-methyltransferase (COMT) gene. Methodology and Findings. Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middleaged men from eastern Finland. A population-based prospective cohort of 792 men aged 46-64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR) of 1.73 (95% confidence interval (CI), 1.07-2.79), and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05-2.77). Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93-2.49), subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50-5.76) as compared with other men. Conclusions. This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels.

Human Biology, 2005

Low levels of high-density lipoprotein (HDL) are widely documented as a risk factor for cardiovas... more Low levels of high-density lipoprotein (HDL) are widely documented as a risk factor for cardiovascular disease (CVD). Furthermore, there

Human Biology, 2005

Pooled DNA samples have been used in association studies of Mendelian disease genes. This method ... more Pooled DNA samples have been used in association studies of Mendelian disease genes. This method involves combining equal quantities of DNA from patients and control subjects into separate pools and comparing the pools for distributions of genetic markers. In this study identical quantities of DNA from 300 individuals representing 6 populations were pooled and amplified for 296 loci using the touchdown polymerase chain reaction (PCR) method. The purpose of this study is to test the efficacy of pooled DNA markers in the reconstruction of the genetic structure of human populations. The populations sampled included Chuvash, Buryats, Kizhi, Native Americans, South Africans, and New York City whites. To test the accuracy of the allele-frequency distributions, we genotyped the Buryats and New York samples individually for six microsatellite markers and compared their frequencies to the allele frequencies derived from the electropherogram peak heights for the pooled DNA, producing a correlation of 0.9811 with a variance of less than 0.04. Two-dimensional scaling of genetic distances among the six populations produced clusters that reflected known historical relationships. A distance matrix was created using all 296 loci, and matrices based on individual chromosomes were correlated against the total matrix. As expected, the largest chromosomes had the highest correlations with the total matrix, whereas one of the smallest chromosomes, chromosome 22, had the lowest correlation and differed most from the combined STR distance matrix. Genetic markers and their allele frequencies in human populations reflect the evolutionary history and the genetic structure of these aggregates. However,

Human Biology, 2010

We examined mitochondrial DNA (mtDNA) variation in six Mennonite communities from Kansas (Goessel... more We examined mitochondrial DNA (mtDNA) variation in six Mennonite communities from Kansas (Goessel, Lone Tree, Garden View, Meridian, and Garden City) and Nebraska (Henderson) to determine their genetic structure and its relationship to population history. Mitochondrial DNA haplogroup and haplotype information were obtained from blood samples from 118 individuals. Molecular genetic variation was analyzed using diversity measures, neutrality test statistics, spatial analysis of molecular variance (SAMOVA), and multidimensional scaling plots. The Mennonite samples exhibited eight western European mtDNA haplogroups: H, HV0, I, J, K, T, U, and X. Comparable to other populations of European descent, haplogroup H was the most frequent in all six communities and ranged from 35% in Lone Tree to 75% in Old Order Mennonites from Garden City. Fifty-eight different mtDNA haplotypes were found in these groups with only one shared among all six populations. Haplotype diversities varied from 0.81 in Goessel to 0.96 in Henderson and Garden View. Multivariate statistical analysis of these populations indicates that these Anabaptist communities formed new congregations by fissioning along familial lines. Population subdivision of these communities into congregations supports previously documented patterns of fission-fusion. These haploid molecular data provide a more accurate reflection of biological relationships between midwestern Mennonite communities than evidence based on classical genetic markers.

Journal of Archaeological Science: Reports, 2016

Epigenetic mechanisms have been widely studied for the past several decades, yet despite a surfei... more Epigenetic mechanisms have been widely studied for the past several decades, yet despite a surfeit of literature examining animal models and extensive human research associating these mechanisms with pathology, little is known regarding the normal variation among populations or the phenotypic relevance of that variation. Moreover, no one is certain of the evolutionary significance these mechanisms and their underlying machinery. Their structure and function are highly dependent upon dietary intake of indispensable nutrients, yet nutrient profiles vary across populations and generations in an ongoing manner and energy intake can fluctuate dramatically. Here, we examine how the DNA methylation might archive ancestral dietary patterns and discuss the initial findings in a pilot study on population variation in DNA methylation patterns in four maternal/offspring duos from three continents (n = 88). This pilot examined DNA methylation patterns across the core promoter of the metabolic gene leptin (LEP), a leading regulator of energy homeostasis and adipogenesis. Remarkably similar overall mean patterns were present across 7 CpG sites which include the C/EBPα transcription binding site, and two sites proximal to the TATA. Findings suggest a stable and conserved DNA methylation pattern in this region of the (LEP) promoter across populations consuming diets from varying food chains.

abstract DNA methylation is the most widely studied of epigenetic mechanisms, with environmental ... more abstract DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process. Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative functions include regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism, and reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examined the significance of variation in DNA methylation patterns along the leptin core promoter in four populations (phase 1) and used biomarkers reflecting leptin's functional process in two of those populations, western Buryat of Siberia and the Mennonite of central Kansas, to investigate the relevance of the ethnic variation identified in the DNA methylation (phase 2). LEP's core promoter region contains both the binding site for C/EBPα (CCAAT/enhancer binding protein alpha), which tempers the final step in adipocyte maturity and capacity to synthesize leptin, and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, suggesting tissue-specific methylation variation at this region (Melzner et al. 2002). We hypothesized that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers that reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system, and anthropometric measures.

An Evolutionary Perspective, 2000