Introduction to the Special Issue: Human Linkage Studies for Behavioral Traits

In the post Genome era, the aim of behavior genetics has shifted from estimating the relative contributions of genes and environmental factors to (co-)variation in human complex traits, to localization of genes and identification of functional genetic variants. This special issue reflects this transition and presents fifteen papers that report on genome-wide linkage scans for complex traits in humans and on methodological tools and innovations. Six papers focus on cognition and report overlapping linkage peaks on chromosomes 6p and 14p. Papers on addictive behavior, i.e. smoking and alcohol dependence and its endophenotypes, find moderate LOD scores on chromosomes 6p, 5q, 4p and 7q, respectively. Three papers concentrate on emotionality, depression and loneliness and examine chromosomes 2q and 12q. The papers in this issue represent a summary of the first large scale linkage enterprises of human behavioral traits. © 2006 Springer Science+Business Media, Inc.link_to_subscribed_fulltex

Laser-UV-microirradiation of interphase nuclei and posttreatment with caffeine: a new approach to establish the arrangement of interphase chromosomes

Laser UV microirradiation of Chinese hamster interphase cells combined with caffeine post-treatment produced different patterns of chromosome damage in mitosis following irradiation of a small area of the nucleus that may be classified in three categories: I) intact metaphase figures, II) chromosome damage confined to a small area of the metaphase spread, III) mitotic figures with damage on all chromosomes. Category III might be the consequence of a non-localized distortion of nuclear metabolism. By contrast, category II may reflect localized DNA damage induced by microirradiation, which could not be efficiently repaired due to the effect of caffeine. If this interpretation is right, in metaphase figures of category II chromosome damage should occur only at the irradiation site. The effect might then be used to investigate neighbourhood relationships of individual chromosomes in the interphase nucleus

Sex chromosome positions in human interphase nuclei as studied by in situ hybridization with chromosome specific DNA probes

Two cloned repetitive DNA probes, pXBR and CY1, which bind preferentially to specific regions of the human X and Y chromosome, respectively, were used to study the distribution of the sex chromosomes in human lymphocyte nuclei by in situ hybridization experiments. Our data indicate a large variability of the distances between the sex chromosomes in male and female interphase nuclei. However, the mean distance observed between the X and Y chromosome was significantly smaller than the mean distance observed between the two X-chromosomes. The distribution of distances determined experimentally is compared with three model distributions of distances, and the question of a non-random distribution of sex chromosomes is discussed. Mathematical details of these model distributions are provided in an Appendix to this paper. In the case of a human translocation chromosome (XqterXp22.2::Yq11Y qter) contained in the Chinese hamster x human hybrid cell line 445 x 393, the binding sites of pXBR and CY1 were found close to each other in most interphase nuclei. These data demonstrate the potential use of chromosome-specific repetitive DNA probes to study the problem of interphase chromosome topography

Studies on the clinical significance of nonesterified and total cholesterol in urine

Gas-liquid chromatographic determinations of nonesterified and total urinary cholesterol were performed in 137 normals, 264 patients with various internal diseases without evidence of neoplasias or diseases of the kidney or urinary tract, 497 patients with malignancies and 236 patients with diseases of the kidney, urinary tract infections or prostatic adenoma with residual urine. A normal range (mean±2 SD) of 0.2–2.2 mg/24 hours nonesterified cholesterol (NEC) and of 0.3–3.0 mg/24 hours total cholesterol (TC) was calculated. Values of urinary cholesterol excretion were independent of age and sex and did not correlate with cholesterol levels in plasma. Patients with various internal diseases, without evidence of neoplasias nor diseases of the kidney or obstruction of the urinary tract, showed normal urinary cholesterol excretions, as did patients with infections of the urinary tract. However, elevated urinary cholesterol was found in patients with diseases of the kidney or urinary tract obstruction (prostatic adenoma with residual urine), malignant diseases of the urogenital tract and metastasing carcinoma of the breast. In patients with other malignant diseases urinary cholesterol was usually normal. Lesions of the urothelial cell membranes are considered to be the most likely cause of urinary cholesterol hyperexcretion. The clinical value of urinary cholesterol determinations as a possible screening test for urogenital carcinomas in unselected populations is limited by lacking specificity, expensive methodology and low prevalence of the mentioned carcinomas, although elevated urinary cholesterol excretions have been observed in early clinical stages of urogenital cancers

Inherited electrophoretic variants detected in a Japanese population with two-dimensional gels of erythrocyte lysates

Genetic variation has been studied in erythrocyte lysates from 100 Japanese children and their parents by means of two-dimensional polyacrylamide gel electrophoresis. Fifty-five polypeptides selected without respect to variability were considered suitable for scoring. Genetic variation was encountered in 14 of these polypeptides. Family data show that the segregation of 13 variants is consistent with an autosomal codominant mode of inheritance; the remaining variant exhibits a sex-linked mode of inheritance. Of 8 presumably identical polypeptides found variable in Japanese and/or Caucasians, differences in the occurrence or allele frequencies of polymorphisms were recognized for four. Contrary to the experience of some investigators, the amount of variation and the ethnic differences we are encountering indicate that two-dimensional polyacrylamide gel electrophoresis is a sensitive tool for the study of genetic events.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65555/1/j.1469-1809.1986.tb01753.x.pd

Family composition and age at menarche: findings from the international Health Behaviour in School-Aged Children Study

This research was funded by The University of St Andrews and NHS Health Scotland.Background Early menarche has been associated with father absence, stepfather presence and adverse health consequences in later life. This article assesses the association of different family compositions with the age at menarche. Pathways are explored which may explain any association between family characteristics and pubertal timing. Methods Cross-sectional, international data on the age at menarche, family structure and covariates (age, psychosomatic complaints, media consumption, physical activity) were collected from the 2009–2010 Health Behaviour in School-aged Children (HBSC) survey. The sample focuses on 15-year old girls comprising 36,175 individuals across 40 countries in Europe and North America (N = 21,075 for age at menarche). The study examined the association of different family characteristics with age at menarche. Regression and path analyses were applied incorporating multilevel techniques to adjust for the nested nature of data within countries. Results Living with mother (Cohen’s d = .12), father (d = .08), brothers (d = .04) and sisters (d = .06) are independently associated with later age at menarche. Living in a foster home (d = −.16), with ‘someone else’ (d = −.11), stepmother (d = −.10) or stepfather (d = −.06) was associated with earlier menarche. Path models show that up to 89% of these effects can be explained through lifestyle and psychological variables. Conclusions Earlier menarche is reported amongst those with living conditions other than a family consisting of two biological parents. This can partly be explained by girls’ higher Body Mass Index in these families which is a biological determinant of early menarche. Lower physical activity and elevated psychosomatic complaints were also more often found in girls in these family environments.Publisher PDFPeer reviewe

Holocentric Chromosomes of Luzula elegans Are Characterized by a Longitudinal Centromere Groove, Chromosome Bending, and a Terminal Nucleolus Organizer Region

The structure of holocentric chromosomes was analyzed in mitotic cells of Luzula elegans. Light and scanning electron microscopy observations provided evidence for the existence of a longitudinal groove along each sister chromatid. The centromere-specific histone H3 variant, CENH3, colocalized with this groove and with microtubule attachment sites. The terminal chromosomal regions were CENH3-negative. During metaphase to anaphase transition, L. elegans chromosomes typically curved to a sickle-like shape, a process that is likely to be influenced by the pulling forces of microtubules along the holocentric axis towards the corresponding microtubule organizing regions. A single pair of 45S rDNA sites, situated distal to Arabidopsis-telomere repeats, was observed at the terminal region of one chromosome pair. We suggest that the 45S rDNA position in distal centromere-free regions could be required to ensure chromosome stability. Copyright (C) 2011 S. Karger AG, Base

Trend-TDT – a transmission/disequilibrium based association test on functional mini/microsatellites

<p>Abstract</p> <p>Background</p> <p>Minisatellites and microsatellites are associated with human disease, not only as markers of risk but also involved directly in disease pathogenesis. They may play significant roles in replication, repair and mutation of DNA, regulation of gene transcription and protein structure alteration. Phenotypes can thus be affected by mini/microsatellites in a manner proportional to the length of the allele. Here we propose a new method to assess the linear trend toward transmission of shorter or longer alleles from heterozygote parents to affected child.</p> <p>Results</p> <p>This test (trend-TDT) performs better than other TDT (Transmission/Disequilibrium Test) type tests, such as TDT_maxand TDT_L/S, under most marker-disease association models.</p> <p>Conclusion</p> <p>The trend-TDT test is a more powerful association test when there is a biological basis to suspect a relationship between allele length and disease risk.</p

Smoking as a product of gene–environment interaction

A strong hereditary influence on smoking has been demonstrated. As one of the candidate genes in relation to smoking, the serotonin transporter gene (5-HTTLPR) has been suggested, however with conflicting results. In recent studies, it has been shown that genotypic and environmental (G*E) factors interact in the shaping of a variety of phenotypic expressions. The objective of the present study was to investigate the interaction between a variation in the 5-HTTLPR and family environment in relation to smoking habits, nicotine dependence, and nicotine and cotinine levels in hair samples