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PubMed2005

Genome-wide scans for loci under selection in humans.

Natural selection, which can be defined as the differential contribution of genetic variants to future generations, is the driving force of Darwinian evolution. Identifying regions of the human genome that have been targets of natural selection is an important step in clarifying human evolutionary history and understanding how genetic variation results in phenotypic diversity, it may also facilitate the search for complex disease genes. Technological advances in high-throughput DNA sequencing and single nucleotide polymorphism genotyping have enabled several genome-wide scans of natural selection to be undertaken. Here, some of the observations that are beginning to emerge from these studies will be reviewed, including evidence for geographically restricted selective pressures (ie local adaptation) and a relationship between genes subject to natural selection and human disease. In addition, the paper will highlight several important problems that need to be addressed in future genome-wide studies of natural selection.

Chromosome Mapping↗
PubMed2000

Etiology of neuroanatomical correlates of reading disability.

The heritable nature of reading disability has been well documented (DeFries & Alarcón, 1996), and possible abnormalities of brain structures have been associated with the disorder (Filipek, 1995). However, the etiology of individual differences in morphological brain measures has not been examined extensively. The purpose of this study was to apply behavioral genetic methods to assess the etiology of individual differences in neuroanatomical structures. Measures of reading performance, cognitive ability, and magnetic resonance imaging scans were obtained from 25 monozygotic (MZ) and 23 same-sex dizygotic (DZ) twin pairs with reading disability, and 9 MZ and 9 DZ control twin pairs participating in the Colorado Learning Disabilities Research Center. Results obtained from multiple regression analyses (DeFries & Fulker, 1985, 1988) of these twin data indicated that individual differences in the size of most cortical and subcortical structures were largely due to heritable influences. Moreover, estimates of heritability did not change appreciably after controlling for IQ and total brain size.

Adolescent↗
PubMed1979

A funny thing happened to us on the way to the latent entities.

Inferred latent entities, whether those of psychoanalysis, factor analysis, or cluster analysis, have declined in value for many clinical psychologists, both as tools of practice and as objects of theoretical interest. Behavior modification, rational-emotive therapy, crisis intervention, psycho-pharmacology, and actuarial prediction all tend to minimize reliance on latent entities in favor of purely dispositional concepts. Behavior genetics is, however, a powerful movement to the contrary. As regards categorical entities (types, taxa, syndromes, diseases), history reveals no impressive examples of their discovery by cluster algorithms; whereas organic medicine and psychopathology have both discovered many taxonic entities without reliance on formal (statistical) cluster methods. I offer eight reasons for this strange condition, with associated suggestions for ameliorating it. Adopting a realist instead of a fictionist approach to taxonomy, I give high priority to theory-based mathematical derivation of quantitative consistency tests for all taxometric results. I urge a large scale cooperative survey of taxometric methods based on Monte Carlo runs, biological pseudoproblems where the true axon is independently known, and live problem in genetics, organic medicine, and psychopathology. An empirical example of taxometric bootstrapping and consistency testing was presented from my own current research on schizotypy.

Humans↗
PubMed1989

10T1/2 cells: an in vitro model for molecular genetic analysis of mesodermal determination and differentiation.

Progress has been made in understanding the molecular mechanisms that regulate cell type-specific gene expression during the terminal differentiation of cells into specialized tissue types. These studies have concentrated largely on defining the cis elements and trans-acting factors responsible for the transcription of differentiation-specific genes. Valuable as these investigations have been, they have not been able to place differentiation into the larger context of development, specifically into the context of the earlier developmental process of cell determination, when embryonic stem cell lineages are formed and the genetic regulatory programs for cell type-specific gene activation and expression are acquired by stem cells. The clonal mouse embryo cell line, C3H/10T1/2, clone 8 (10T1/2) provides a unique opportunity to examine the molecular genetic regulation of both the developmental determination of vertebrate stem cell lineages and their subsequent differentiation. 10T1/2 is an apparently multipotential cell line that can be converted by 5-azacytidine into three mesodermal stem cell lineages. These determined proliferative stem cells are stable in culture and retain their ability to differentiate in mitogen-depleted medium. The most significant discovery has been that 10T1/2 lineage determination is under simple genetic control and that the regulatory genes that mediate the formation of myogenic cell lineages, and likely the chondrogenic and adipogenic lineages, can be demonstrated and studied by genomic DNA and cDNA transfection approaches. This paper is a description of the remarkable properties and genetic behaviors of the 10T1/2 cells and a discussion of the insights that future studies of this cell may provide.

Animals↗
PubMed2005

Where did I leave my keys? A twin study of self-reported memory ratings using the multifactorial memory questionnaire.

Behavior genetics has convincingly shown the importance of genetic factors in objective tests of memory function. However, self-report memory tests have received little attention. This study used items from the Multifactorial Memory Questionnaire (MMQ) to estimate the heritability of self-reported memory contentment and ability in 909 monozygotic (MZ) and 1034 dizygotic (DZ) twin pairs aged between 20 and 84 years from the St Thomas' Adult UK Twin Register. Heritability estimates ranged between 37% and 64% for contentment (e.g., reporting to worry about one's memory) and approximately 45% for ability (e.g., reporting a tendency to forget keys). Shared family environmental influences (between 32% and 33%) were found for some abilities (e.g., learning to use a new gadget). Given their clinical significance and ease of administration, these tests could prove to be useful in examining memory functioning in large-scale population studies.

Adult↗
PubMed2005

Personality disorder research agenda for the DSM-V.

The American Psychiatric Association is sponsoring a series of international conferences to set a research agenda for the development of the next edition of the diagnostic manual. The first conference in this series, "Dimensional Models of Personality Disorder: Etiology, Pathology, Phenomenology, and Treatment," was devoted to reviewing the existing research and setting a future research agenda that would be most effective in leading the field toward a dimensional classification of personality disorder. The purpose of this article, authored by the Steering Committee of this conference, was to provide a summary of the conference papers and their recommendations for research. Covered herein are the reviews and recommendations concerning alternative dimensional models of personality disorder, behavioral genetics and gene mapping, neurobiological mechanisms, childhood antecedents, cross-cultural issues, Axes I and II continuity, coverage and cutoff points for diagnosis, and clinical utility.

Congresses as Topic↗
PubMed2005

No patrigenes required for femaleness in the haplodiploid wasp Nasonia vitripennis.

The parasitoid wasp Nasonia vitripennis is an emerging model organism for developmental and behavioral genetics. It reproduces by haplodiploidy; males typically develop parthenogenetically from haploid eggs and females from fertilized diploid eggs. A polyploid mutant strain is available in which females are triploid and lay haploid and diploid eggs that normally develop into males when unfertilized. In contrast to previous reports, approximately 2% of triploid females were found to occasionally produce daughters as well as gynandromorphs from diploid unfertilized eggs. Daughter production increased with age and differed among familial lineages. This is the first report of parthenogenetic female development in Nasonia. The results show that a paternally provided genome is not required for femaleness and call for modifications of existing models of sex determination in Nasonia.

Animals↗
PubMedDate not supplied

[Community genetics and hemophilia in a Brazilian population].

Hemophilia is an important hemorrhagic disease in Brazil, affecting about 1 out of every 10,000 males. Patient's self-perception of hemophilia and interaction with the community are relevant to the clinical management of this disease. We investigated several social, psychological, and community aspects of hemophilia in a Brazilian population (Campinas, São Paulo State), interviewing 30 hemophiliac males, a control sample comprised of 73 non-hemophiliac brothers, and 641 individuals from the community. According to our results, more severe social disability in the hemophiliac patient was related to economic factors, mainly unemployment; however, no difference was found in relation to marital status, reproduction, or education. Self-perception of changes in health and lifestyle by individuals with hemophilia showed frequent self-stigmatization, along with depression, anxiety, and insecurity. The community showed a widespread lack of familiarity with hemophilia (49%), viewing people with hemophilia with the kinds of prejudices often observed in relation to people with infectious diseases, like AIDS. The paper concludes by recommending that a community-based program be implemented to improve the social adjustment status of individuals with hemophilia.

Adult↗
PubMed1991

Prevalence of diabetes in Mexican Americans, Cubans, and Puerto Ricans from the Hispanic Health and Nutrition Examination Survey, 1982-1984.

The purpose of this study was to estimate the prevalence of diagnosed and undiagnosed diabetes among Mexican Americans, Cubans, and Puerto Ricans in the United States and compare these estimates to data from prior surveys for U.S. non-Hispanic whites and blacks. Data for this study are from the Hispanic Health and Nutrition Examination Survey, a multipurpose cross-sectional survey of three U.S. Hispanic populations conducted in 1982-1984. The interviewed sample of people aged 20-74 yr included 3935 Mexican Americans in the southwest, 1134 Cubans in Florida, and 1519 Puerto Ricans in the New York City area. The diabetes component consisted of interview questions on diabetes diagnosis and treatment and an oral glucose tolerance test administered to a subsample. The prevalence of diabetes was two to three times greater for Mexican Americans and Puerto Ricans than for non-Hispanic whites surveyed in 1976-1980. In Cubans, the prevalence was similar to that for non-Hispanic whites. In men and women 45-74 yr of age, the prevalence of diabetes was extremely high for both Mexican Americans (23.9%) and Puerto Ricans (26.1%) compared with Cubans (15.8%) or non-Hispanic whites (12%). The total prevalence of diabetes was not significantly different for Mexican Americans and Puerto Ricans but was significantly lower for Cubans. The relatively lower prevalence of diabetes among Cubans and the high prevalence in both Mexican Americans and Puerto Ricans may be related to socioeconomic, genetic, behavioral, or environmental factors.

Adult↗
PubMed1993

Brain, environment, heredity, and personality.

Behavior genetics research, committed to a model of the origins of personality and intellectual development restricted to heredity and environment, consistently generates evidence for two types of environmental influences. One of these, termed the between-family or shared environment, creates no conceptual problems. The other, termed the nonshared or within-family or unique environment, does. The other, termed the nonshared or within-family or unique environment, does. The latter accounts for a substantial portion of the variance in personality and intellect, it must be unique to each individual, and its origin has not been determined. It is contended here that the brain itself, as an inherently indeterminate dynamic system, is the source of this unresolved developmental variability.

Animals↗
PubMed1993

Identification of linotte, a new gene affecting learning and memory in Drosophila melanogaster.

We describe the identification of linotte, a new autosomal gene in Drosophila involved with learning and memory. The linotte mutant was derived from a PlacW transposon mutagenesis and was screened for three-hour memory deficits after classical conditioning of an olfactory avoidance response. Sensory and motor systems (olfactory acuity and shock reactivity) required for the classical conditioning experiments were normal in mutant linotte flies--indicating that the mutation disrupts learning/memory specifically. A chromosomal deficiency of the 37D region, where the linotte P insert was localized in situ, failed to complement linotte's memory defect, and flies from two lines homozygous for independent PlacW excisions show normal memory--indicating that the P insertion is responsible for the mutant phenotype. Additional behavior-genetic data suggest that linotte gene is non-vital.

Animals↗
PubMed2003

Extending SEE for large-scale phenotyping of mouse open-field behavior.

SEE (Software for the Exploration of Exploration) is a visualization and analysis tool designed for the study of open-field behavior in rodents. In this paper, I present new extensions of SEE that were designed to facilitate its use for mouse behavioral phenotyping and, especially, for the problems of discrimination of genotypes and the replication of results across laboratories and experimental conditions. These extensions were specifically designed to promote a new approach in behavioral phenotyping, reminiscent of the approach that has been successfully employed in bioinformatics during recent years. The path coordinates of all animals from many experiments are stored in a database. SEE can be used to query, visualize, and analyze any desirable subsection of this database and to design new measures (endpoints) with increasingly better discriminative power and replicability. The use of the new extensions is demonstrated here in the analysis of results from several experiments and laboratories, with an emphasis on this approach.

Animals↗
PubMed2005

Epidemiology of osteoarthritis.

The majority of adults > 55 years of age show radiographic evidence of osteoarthritis; however, determining definitive prevalence and incidence rates of knee osteoarthritis and hip osteoarthritis poses methodologic problems. Several factors play a role in osteoarthritis risk, including age, gender, genetics, behavioral influences, and ethnicity. Studies cited compare data from the Framingham Osteoarthritis Study with data from studies performed in Asian and European populations. A number of broad trends stand out, including higher prevalence in advanced age for both hip and knee osteoarthritis, with higher prevalence and incidence in women than in men.

Age Factors↗
PubMedDate not supplied

Spatiotemporal structure of olfactory inputs to the mushroom bodies.

A requirement to understand mushroom body (MB) function is to characterize the operations (or transformations) that they impose on incoming signals. Understanding the nature of these integrative operations requires an understanding of the inputs from other brain areas. By inputs we mean not only the anatomical pathways leading to the MBs, but also the dynamic structure of the inflow of sensory (and other) signals. Neurons are complex, capacitative, and generally nonlinear devices that transform barrages of neurochemical packets into electrical waveforms. Their modes of operation are intrinsically time dependent and therefore, their functions or roles in a circuit cannot be inferred only from structural data. Thanks to elegant anatomical, behavioral, genetic, and molecular (for review, see Crittenden et al. 1998; Hammer and Menzel 1998; Heisenberg 1998; Wolf et al. 1998) studies, there is convincing evidence that MB circuits are involved, at least in fruit flies and honeybees, in some forms of odor integration and learning. In vivo electrophysiological studies of MB neurons, however, are rare and mainly restricted to individual (or small populations of) so-called extrinsic neurons, that is, those whose processes link MBs with other brain areas (Schildberger 1983, 1984; Homberg 1984; Hammer 1993; Mauelshagen 1993; Li and Strausfeld 1997). Kaulen et al. (1984) examined extracellular potentials in the MBs of bees, using current source density analysis, and more recently, Laurent and Naraghi (1994) provided a description of stimulus-evoked activity in Kenyon cells (KCs), the intrinsic neurons of the MBs, using intracellular recordings. In this short review we will summarize the recent results from our laboratory in an attempt to provide a description of the spatiotemporal structure of olfactory inputs to the MBs and their intrinsic neurons. We will focus only on the encoding of odor quality. We will then speculate on the possible role of MB circuits for olfactory processing.

Animals↗