Quantitative trait loci (QTL) for circadian rhythms of locomotor activity in mice

The loomotor activity of male mice (Mus musculus) was monitored by infrared photoelectric beams under three lighting regimens: LD (12 h of light and 12 h of dark), DD (constant dark), and LL (constant broad-spectrum light, 10 lux). Circadian period of locomotor activioty (τ) was compared among 3 inbred strains of mice, C57BL/6J (B6), BALB/c (C), and DBA/2J (D2), and 26 recombinant inbred strains B×D (B6×D2). the τ under both continuous low-intensity light and continuous darkenss varied significantly among strains. Under DD the mean τ was 23.8 h for B6, 23.7 h for D2, and 23.6 h for C. Under LL the mean τ was 25.1 for B6, 23.9 h for D2, and 25.5 h for C. Frequency histograms of the mean τ of 26B×D RI mouse strains (three to seven animals per strain) in either DD or LL and the difference between them, Δτ, had distributions which appeared unimodal, suggesting polygenic inheritances. The narrow-sense heritability determined using 26 strains of B×D RI mice was about 55% for τ and about 38% for both τ in LL and Δτ. An estimated four loci contribute to the variance of τ in constant darkness and five to the variance of τ in constant low-intensity light among the strains studied. Quantitative trait locus (QTL) analysis identified several potential genetic loci associated with τ in constant darkness, τ in constant low-intensity light, and Δτ. The associations of highest probability for each of these traits were theD1Nds4 locus (p<0.001) on mouse chromosome 1, theD5Ncvs52 locus (p<.05) on mouse chromosome 5, and thePmv12 locus (p<.01) at 70 cM on mouse chromosome 5, respectively. A QTL identified for τ was associated (p<.05) with theD2NDS1 marker at 45 cM on chromsome 2 near the Ea 6 marker at 46 cM associated (p<.05) with that reported for the period of wheel running activity in seven C×B RI strains (Schwartz, W. J., and Zimmerman, P.,J. Neurosci. 10:3685 1990).     

Genetic alterations in primary and secondary hyperparathyroidism

Hyperparathyroidism refers to a term representing a wide spectrum of parathyroid disorders that are characterized by the increased production of parathyroid hormone. Hyperparathyroidism was once thought to be tare but is now more commonly recognized, aifecting 1 in 500 women over 40 years of age. Yet the interpretation of parathyroid pathology is still controversial and confusing. Over the past 10 years, genetic changes ( ret and menin genes) involved in the pathogenesis of MEN 2 and MEN 1 have been discovered in succession. Different mutations of the calcium-sensing receptor gene have been identified in neonatal severe hyperparathyroidism and familial hypocalciuric hypercal-cemia, respectively. The HRPT 2 gene responsible for the development of heredltaty hyperparathyroidism and jaw tumors has been localized on the 1q21–31 locus. Several genetic alterations have also been characterized in primary and secondary hyperparathyroidism. Different genetic alterations appear to involve the development of different types of hyperparathyroidism. These novel advances give us new insights into the pathogenesis of hyperparathyroidism and allow better differentiation between the different types of parathyroid disorders.     

A Diagnostic Approach to Adrenal Cortical Lesions

The adrenal gland is not a common specimen in surgical pathology practice as, until recently, adrenal tumors were recognized in life only if associated with hypersecretion of hormones or evidence of malignancy. However, adrenal nodules are not uncommon at autopsy, and the number of these found in life is now increasing as they are identified when the abdomen is scanned for the investigation of other diseases using computed tomography or magnetic resonance imaging. It is therefore becoming increasingly important for the surgical pathologist to be aware of the range of pathology in the gland and to understand how to approach the specimens. This short review will deal with lesions of the adrenal cortex.     

The Society for Craniofacial Genetics and Developmental Biology 41st Annual Meeting

The mission of the Society for Craniofacial Genetics and Developmental Biology (SCGDB) is to promote education, research, and communication about normal and abnormal development of the tissues and organs of the head. The SCGDB welcomes as members undergraduate students, graduate students, postdoctoral researchers, medical and dental practitioners, scientists, and academicians who possess an interest in craniofacial biology. Each year our members come together to share their novel findings, build upon, and challenge current knowledge of craniofacial biology.     

A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia

Eight mutations in the gene (the RYR1 gene) encoding the calcium release channel of sarcoplasmic reticulum (SR) in skeletal muscle are so far known to be very closely linked to malignant hyperthermia susceptibility in man and are regarded to be causative. We have examined 41 Swedish families where malignant hyperthermia had occurred in at least one member during anaesthesia, with respect to three of the known mutations. The mutations were Arg163Cys; Ile403Met and Arg614Cys (also known as the "pig mutation"). In three (i.e. 7%) of the families we detected the Arg614Cys mutation, and this was the only one of the mutations searched for that was observed. This indicates that other mutations than those searched for in this study must cause malignant hyperthermia susceptibility in most Swedish malignant hyperthermia susceptible families.     

Bloom''s Syndrome. VII. Progress report for 1978

The Bloom's Syndrome Registry was published in this journal in 1977. Now, in the first in a series of progress reports, recent accessions to the Registry are recorded, new instances of neoplasia are listed, and recent clinical observations and experimental results of general interest are cited.     

Recombinant congenic strains of mice from B10.D2 and DBA/2: Their contribution to behavior genetic research and application to audiogenic seizures

Recombinant congenic strains (RCS) represent a series of related strains, each of which carries a small fraction of the genome of one strain (donor strain) on the genetic background of another strain (background strain). Recombinant inbred strains (RIS) are commonly used to identify major gene segregation and linkage and associations between behavior and quantitative trait loci, whereas recombinant congenic strains (RCS) open other complementary leads. The variability in the reactivity of RCS to a trait is thus the expression of few minor-effect genes originating from the donor strain, because the probability that major genes are present in any one RCS is low. Unlike RIS in which minor-effect genes are often masked by major genes, RCS enable the effects of minor genes to be studied. With our method, for a given trait, an estimate can be made of the gene strength distribution as well as an estimate of the minimal number of genes involved having a certain strength.This study was supported by the Centre National de la Recherche Scientifique (URA 1924 and CSEAL-UPS 44, CNRS), Université René-Descartes, Paris V UFR Biomédicale, and the Fondation pour la Recherche Médicale.     

Risk of obstetric cholestasis in sisters of index patients

The aim of the present study was to evaluate the rate of intrahepatic cholestasis of pregnancy in first-degree relatives of index patients. Index patients (n=65) with singleton pregnancies complicated by intrahepatic cholestasis were identified among the women (n=11 984) who gave birth at Kuopio University Hospital in 1994-1998. The pregnancy histories of relatives of 56 index patients were reviewed and the rate of cholestasis in first-degree relatives was compared with that in the general obstetric population. Obstetric cholestasis was experienced by 9% of the parous sisters and 11% of the mothers of the index patients. The risk per delivery was 6% in the first-degree relatives. The rate in the general obstetric population was 0.54%. The odds ratios and 95% confidence intervals were 12.6 (5.6-28.1) for the sisters and 12.2 (6.2-24.2) for the mothers. Obstetric cholestasis clusters within some families and is under strong genetic influence, although the precise genetic pattern remains obscure. The sisters of index patients are at an increased risk of the disorder and may benefit from close obstetric care.     

Male mating speed as a component of fitness inDrosophila

From a survey of published data on the genusDrosophila, it is clear that male mating speed or male virility is probably the most important component of fitness. Rapid matings tend to be controlled by the male genotype, while the genotype of the female may assume importance for slower matings. Where data exist, male mating speed is subject to directional selection in the direction of rapid speed, as would be expected for an important component of fitness.Supported by the Australian Research Grants Committee.