Diddahally Govindaraju

Archibald Garrod (1857–1936) is best remembered for introducing Mendelian inheritance into medicine and for his book, “Inborn Errors of Metabolism.” Garrod appreciated that inborn errors were products of our evolutionary history. The recognition of inborn errors led Garrod to the broader concept of chemical individuality. Chemical individuality, wh...

This encyclopedia brings together a comprehensive collection of work highlighting established research and emerging science in all relevant disciplines in gerontology and population aging. It covers the breadth of the field, gives readers access to all major sub-fields, and illustrates their interconnectedness with other disciplines. With more than...

We have identified a chloroplast DNA polymorphism that separates shortleaf, slash, longleaf, and loblolly pines into three groups. Although little intraspecific variation was evident, the marker was polymorphic in slash pine. This marker may be useful for monitoring interspecific hybridization and introgression in the southern pines.

A cloned, 500 base pair (bp) restriction fragment from the chloroplast genome of Pinus contorta hybridized to restriction fragments of a previously known polymorphism when used in molecular mapping experiments with total cellular DNAs of P. banksiana and P. contorta. Unexpectedly however, a large number (as many as 20) of additional, extremely poly...

A chloroplast DNA restriction fragment length polymorphism (RFLP) and its relationship with cone morphology was studied in a sympatric population of lodgepole pine and jack pine. Novel cpDNA variants, found only in or near the sympatric region, occurred in approximately 5% of the individuals of this population. Chloroplast DNA typical of jack pine...

The predictability of stability indices at different developmental stages of seedling growth was studied in forty open-pollinated families of jack pine (Pinus banksiana Lamb.). Two sets of studies were conducted simultaneously under greenhouse conditions. In the first, the seeds were germinated under four levels of water stresses; in the second, th...

A knowledge of relationship coefficients has been suggested to be of critical importance in making a decision on choice of selection method from natural populations of forest trees. Data on population structure of several coniferous and angiosperm forest trees were utilized to obtain relationship coefficients. The results suggested that relationshi...

How aging is influenced by the sequential accumulation of both inherited and somatic mutaions

Abstract Ken Burns, a well-known documentarian has produced a film titled, “The Gene: An Intimate History” based on Siddhartha Mukherjee’s book by the same name. The film focuses sharply on the history of genetics, the science of inheritance and variation, in particular, the gene, the central player in genetics, its discovery, structure and functio...

Mutation accumulation has been proposed as a cause of senescence. During this process, age-related genetic and epigenetic mutations steadily accumulate. Cascading deleterious effects of mutations might initiate a steady “accumulation of deficits” in cells, despite the existence of repair mechanisms, leading to cellular senescence and functional dec...

Aging entails an irreversible deceleration of physiological processes, altered metabolic activities, and a decline of the integrity of tissues, organs, and organ systems. The accumulation of alterations in the genetic and epigenetic spaces has been proposed as an explanation for aging. They result, at least in part, from DNA replication and chromos...

Recognition and exploitation of hybrid vigor or heterosis among individual crosses of plants and animals has a long and distinguished history. Its manifestation is influenced by a combination of genetic, epigenetic, phenotypic, and environmental factors. Although heterosis is known to be governed by both dominant and epistatic gene action, its expr...

Mutation accumulation has been proposed as a cause of senescence. In this process, both constitutional and recurrent mutations accumulate gradually and differentially among differentiating cells, tissues and organs, in relation to stage and age, analogous to Muller’s ratchet in asexually reproducing organisms. Latent and cascading deleterious effec...

Although both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) signaling were shown to regulate life span in lower organisms, the role of GH signaling in human longevity remains unclear. Because a GH receptor exon 3 deletion (d3-GHR) appears to modulate GH sensitivity in humans, we hypothesized that this polymorphism could play a role i...

Mukherjee, S. The Gene: An intimate history.Scribner, NY.594 pages; ISBN: 978-1-4767-330-0; Price: $20.00.

Aging involves a progressive decline of metabolic function and an increased incidence of late-onset degenerative disorders and cancer. To a large extent, these processes are influenced by alterations affecting the integrity of genome architecture and, ultimately, its phenotypic expression. Despite the progress made towards establishing causal links...

Archibald E. Garrod: the father of precision medicine Robert L. Perlman, MD, PhD1 and Diddahally R. Govindaraju, PhD In his 2015 State of the Union address, President Obama launched the Precision Medicine Initiative (PMI). In brief, the goal of this ambitious initiative is to improve health by tailoring the prevention and treatment of disease to g...

All biological variation is hierarchically organized dynamic network system of genomic components, organelles, cells, tissues, organs, individuals, families, populations and metapopulations. Individuals are axial in this hierarchy, as they represent antecedent and attendant aspects of health, disease, evolution and medical care. Humans show individ...

Individual vs family/group slection in natural populations of forest trees

Senescence, as a time-dependent developmental process, affects all organisms at every stage in their development and growth. During this process, genetic, epigenetic and environmental factors are known to introduce a wide range of variation for longevity among individuals. As an important life-history trait, longevity shows ontogenetic relationship...

Longevity as a complex life-history trait shares an ontogenetic relationship with other quantitative traits and varies among individuals, families and populations. Heritability estimates of longevity suggest that about a third of the phenotypic variation associated with the trait is attributable to genetic factors, and the rest is influenced by epi...

Natural selection defined by differential survival and reproduction of individuals in populations is influenced by genetic, developmental, and environmental factors operating at every age and stage in human life history: generation of gametes, conception, birth, maturation, reproduction, senescence, and death. Biological systems are built upon a hi...

Aging process or senescence affects the expression of a wide range of phenotypic traits throughout the life span of organisms. These traits often show modular, synergistic, and even antagonistic relationships, and are also influenced by genomic, developmental, physiological and environmental factors. The cardiovascular system (CVS) in humans repres...

Because autosomal genes in sexually reproducing organisms spend on average half their time in each sex, and because the traits that they influence encounter different selection pressures in males and females, the evolutionary responses of one sex are constrained by processes occurring in the other sex. Although intralocus sexual conflict can restri...

Massively parallel sequencing technologies have identified a broad spectrum of human genome diversity. Here we deep sequenced and correlated 18 genomes and 17 transcriptomes of unrelated Korean individuals. This has allowed us to construct a genome-wide map of common and rare variants and also identify variants formed during DNA-RNA transcription....

We have studied chloroplast DNA variation within six individual trees of a Pinusbanksiana–P. contorta sympatric region. In each of four trees, chloroplast DNA variation occurred in needle samples obtained from different parts of the crown. It is unclear whether this within-individual variation is due to somatic mutation or to occasional biparental...

We used 20 heterologous probes (representing approximately 78% of the Pinuscontorta Dougl. chloroplast genome) and 16 endonucleases to examine chloroplast DNA restriction fragments from four Pinus L. species of the southeastern United States. Three variable markers, separated from each other by at least 20 kilobase pairs, were detected in a prelimi...

The magnitude of direct influences of five quantitative traits and their relative changes in three open-pollinated families planted at a high density in four substrates was studied using path analysis. The relationships between diameter and total weight as well as crown length and total height were relatively consistent over environments, families,...

A key goal of biology is to understand phenotypic characteristics, such as health, disease and evolutionary fitness. Phenotypic variation is produced through a complex web of interactions between genotype and environment, and such a 'genotype-phenotype' map is inaccessible without the detailed phenotypic data that allow these interactions to be stu...

Are humans currently evolving? This question can be answered using data on lifetime reproductive success, multiple traits and genetic variation and covariation in those traits. Such data are available in existing long-term, multigeneration studies - both clinical and epidemiological - but they have not yet been widely used to address contemporary h...

A model is investigated in which mutations that affect a complex trait (e.g., heart disease) also affect fitness because the trait is a component of fitness or because the mutations have pleiotropic effects on fitness. The model predicts that the genetic variance, and hence the heritability, in the trait is contributed by mutations at low frequency...

Gene duplications alter the genetic constitution of organisms and can be a driving force of molecular evolution in humans and the great apes. In this context, the study of genomic disorders has uncovered the essential role played by the genomic architecture, especially low copy repeats (LCRs) or segmental duplications (SDs). In fact, regardless of...

Evolution and medicine started an immature romance in the late 19th century that broke up amid violent recriminations in the early 20th century. Thereafter, the relationship remained distant until the partners were reintroduced on a more mature basis by Nesse and Williams’ book, Why We Get Sick: The New Science of Darwinian Medicine (1). (See ref....

The principles governing protein evolution under strong selection are important because of the recent history of evolved resistance to insecticides, antibiotics, and vaccines. One experimental approach focuses on studies of mutant proteins and all combinations of mutant sites that could possibly be intermediates in the evolutionary pathway to resis...

Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inherita...

New applications of evolutionary biology in medicine are being discovered at an accelerating rate, but few physicians have sufficient educational background to utilize them fully. This article summarizes suggestions from several groups who have considered how evolutionary biology can be useful in medicine, what physicians should learn about it, and...

Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inherita...

New applications of evolutionary biology in medicine are being discovered at an accelerating rate, but few physicians have sufficient educational background to use them fully. This article summarizes suggestions from several groups that have considered how evolutionary biology can be useful in medicine, what physicians should learn about it, and wh...

Our aims were to demonstrate that natural selection is operating on contemporary humans, predict future evolutionary change for specific traits with medical significance, and show that for some traits we can make short-term predictions about our future evolution. To do so, we measured the strength of selection, estimated genetic variation and covar...

Identification of risk alleles for human behavioral disorders through genomewide association studies (GWAS) has been hampered by a daunting multiple testing problem. This problem can be circumvented for some phenotypes by combining genomewide studies in model organisms with subsequent candidate gene association analyses in human populations. Here,...

Associations between multilocus heterozygosity and fitness traits, also termed heterozygosity and fitness correlations (HFCs), have been reported in numerous organisms. These studies, in general, indicate a positive relationship between heterozygosity and fitness traits. We studied the association between genome-wide heterozygosity at 706 non-synon...

The growth and development of plants is determined by both genetic and environmental factors. In this study, path analysis was employed to investigate the magnitude of developmental variation among six quantitative characters associated with growth in 29 pitch pine (Pinus rigida Mill.) families at Walden Woods, Lincoln, Mass. Seedlings were grown f...

Qualitative and quantitative estimates of gene flow were obtained for fourteen gymnosperm and seven angiosperm forest tree species. High levels of gene flow were prevalent among gymnosperms while these levels varied from high to low among angiosperms. In both groups, species with greater pollen dispersal abilities appear to maintain high levels of...

The extent of genetic variation and the degree of genetic differentiation among seven ethnic populations from Karnataka, India (Bunt, Havyak, Iyengar, Lingayath, Smartha, Vaishya, Vokkaliga), was investigated using four single nucleotide polymorphisms (SNPs: IL-1A 4845, IL-1B 3954, IL-1B 511 and IL-1RA 2018) of the interleukin gene cluster. Allele...

Michael P. Weiner, Stacey B. Gabriel, Claiborne Stephens, eds. 472 pages. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2007. $165.00. ISBN 978–087969780–8. Genetic variation is central to all evolutionary change. Hence, the study of genetic variation spans plant and animal breeding, conservation biology, human genetics, and compara...

This chapter provides an introduction to the Framingham Heart Study and the genetic research related to cardiovascular diseases conducted in this unique population. It briefly describes the origins of the study, the risk factors that contribute to heart disease, and the approaches taken to discover the genetic basis of some of these risk factors. T...

Neighourhood sizes and variance structure were determined for ten North American coniferous forest tree species, using information on seed dispersal, patterns of life history, and demography. A synthetic cohort of reproductive individuals belonging to a critical age group was constructed using normal yield tables. Data on reproductive individuals i...

Geneticists can now use several million markers to discover genes contributing to human disorders. Some findings confirm classical patterns on the extent and distribution of variation among populations. Others, including recombination hotspots, are completely new. Large collaborative projects have shown that linkage disequilibrium patterns vary amo...

Background : Chronic subclinical inflammation is a prominent feature of atherosclerotic disease. The genetic background for this pro-inflammatory state is not well-established. Circulating biomarker concentrations have become attractive candidates to measure disease activity and prognosis. Methods : We examined 2356 single-nucleotide polymorphisms...

Phenotypes for linkage analyses.

Phenotypes for family-based FBAT analyses.

Phenotypes for population-based GEE analyses.

The Framingham Heart Study (FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among the most comprehensively characterized multi-generational studies in the world. Many collected phenotypes have substantial genetic contributors; yet most genetic determinants remain to be identified. Using single nucleotide polymorphism...

Systemic biomarkers provide insights into disease pathogenesis, diagnosis, and risk stratification. Many systemic biomarker concentrations are heritable phenotypes. Genome-wide association studies (GWAS) provide mechanisms to investigate the genetic contributions to biomarker variability unconstrained by current knowledge of physiological relations...

Cardiovascular disease (CVD) and its most common manifestations--including coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF)--are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease (CVD) claims more lives each year than any other disease. Heart disease and stroke ar...

The magnitude of changes within a system of mutually dependent phenotypic variables in jack pine grown under two densities was studied using path analysis. The degree of relationship among morphological characters was found to be a function of density and the relative position of crown among the competing individuals. Path analysis could be used to...

Variation at four single nucleotide polymorphism (SNP) sites of the interleukin 1 (IL1) gene cluster was investigated among 280 unrelated individuals, representing 7 caste groups from the state of Karnataka, India, and one European American community of Boston, Massachusetts. Allele and haplotype frequencies, strength of linkage disequilibrium, and...

Nine hundred and two individuals from two populations in a Pinus banksiana — P. contora sympatric region were classified by restriction fragment length polymorphisms of two polymorphic chloroplast DNA markers. A large number of novel chloroplast DNA variants were identified which have not been observed in the allopatric ranges of the two parental s...

Levels of gene flow, Nm, were calculated for 34 predominantly self-pollinated plants, using information on differentiation among populations, Gst. Gene flow levels varied from 0.01 to 6.55, and departed significantly from a uniform distribution. High, medium and low levels of gene flow were found among 15, 38, and 47 percent of the species, respect...

Patients with fatty acid oxidation (FAO) disorders may die suddenly and unexpectedly during episodes of fasting intolerance. To expand existing protocols for the postmortem diagnosis of FAO disorders, we tested the use of acylcamitine (AC) analysis of bile, a specimen readily available at autopsy. Using electrospray/tandem mass spectrometry, we per...

Fatty acid oxidation (FAO) disorders represent a frequently misdiagnosed group of inborn errors of metabolism. Some patients die at the first episode of fasting intolerance and, if appropriate investigations are not undertaken, often meet the criteria of sudden infant death syndrome (SIDS). To expand existing protocols for the postmortem diagnosis...

We determined the number and distribution of rRNA genes among individuals of eight pitch pine populations representing a small ecosystem. While these populations show little or no variation for allozymes and also experience high gene flow, they exhibit large amounts of morphological diversity, apparently caused by environmental stress. Nine to ten...

Phylogenetic relationships among 30 species of the genusPinus were studied using restriction site polymorphism in the large subunit of nuclear rDNA. Of the 58 restriction sites scored, 48 were phylogenetically informative, and the 30 species reduced to ten taxa when species with identical restriction site patterns were combined. These ten taxa corr...

The spatial distributions of cone morphology and paternally inherited chloroplast DNA variants were studied at two sites in a Pinus banksiana-Pinus contorta sympatric region of natural hybridization. Variants of both polymorphisms were distributed nonrandomly at each location, with several variants arranged in conspicuous clusters. Spatial patterns...

Models of gene flow, selection and demography were employed to determine the minimum limits and amplitudes of seed-collection and seed-transfer zones in forest trees, using loblolly pine (Pinus taeda L.) and white spruce (Picea glauca (Moench.) Voss.) as examples. Seed-collection zones were defined in terms of spatial patterns for polygenic (growth...

The inheritance of chloroplast (cp) DNA in jack pine was studied in the parents and progeny of a 4×4 complete diallel. We conclude that cpDNA is predominantly paternally inherited in jack pine independent of background genotype or direction of cross

The relationship between outcrossing rates, t, and the gene flow parameter, Nm, was studied in 32 species of plants. As expected, a significant positive relationship was found between these variables. The low coefficient of determination, however, suggested that outcrossing rate may underestimate gene flow levels in plant populations.

Data from 115 species of plants on the proportion of total gene diversity due to differences among populations, levels of gene flow, and pollination mechanisms were utilized to test the null hypothesis that dispersal abilities as reflected by pollination mechanisms are not associated with gene flow levels in plants. Results suggest that the average...

The concept of phenotypic stability used in plant breeding was employed to test the relationship among allozyme heterozygosity, growth rate, and homeostasis, using seed germination as a model, in 51 open-pollinated families of jack pine. The seeds were germinated in petri dishes in nine variably stressful environments. Mean radicle length per indiv...

The relationships among allozyme heterozygosity, biomass, and seven components of biomass were studied in fifteen open-pollinated families of jack pine grown on four soil substrates. Most of these relationships were curvilinear, and were found under sub-optimal environments. None of the eight characters showed a consistent relationship with allozym...

The relationship between allozyme heterozygosity and biomass production was studied in 40 open-pollinated families of jack pine (Pinus banksiana Lamb.) from a single stand. These were grown on four different soil media under greenhouse conditions. Average weight of biomass per individual was correlated with the allozyme heterozygosity for each fami...

The predictions of the optimality models by Stearns and Crandall, on the relationship between colonization and life history patterns in forest canopy species were examined on thirty-four coniferous forest tree species of North America. Data on several life historical traits such as, age of flowering, seed size, interval between large seed crops, li...