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PubMed1998

The psychosocial and cognitive impact of Duchenne's muscular dystrophy.

Duchenne's muscular dystrophy (DMD) is the most prevalent and devastating of neuromuscular disorders. Children given this diagnosis not only face inevitable deterioration of physical functioning, but they also become susceptible to emotional/behavioral problems, as well as reduced cognitive functioning and learning problems. This article (1) reviews the emotional/behavioral issues that may impact the child with DMD and the affected child's family members and caregivers; (2) examines the research describing the cognitive and learning issues associated with DMD; (3) provides recommendations for physicians who work with these families; and (4) recommends directions for future research that will help to further elucidate emotional/behavioral issues and cognitive and learning correlates of DMD.

Adolescent↗
PubMed2001

Sample size requirements to control for stochastic variation in magnitude and location of allele-sharing linkage statistics in affected sibling pairs.

Typically, genome scans for complex disease have produced linkage peaks which have proved difficult to replicate in additional independent studies. Here we confirm that this may be due to the large variance in magnitude and position of the linkage statistics when maximized across a region. Simulations suggest that for genes of moderate effect (locus-specific sibling relative risks lambda s in the range 1.23-1.39), sample sizes of less than 500 affected sib pairs will give unacceptably large standard errors in the magnitudes and locations of significant linkage results. For genes of small effect (lambda s < or = 1.13), sample sizes in the region of 1000-2000 pairs may be required to achieve consistency of results between different studies. These figures have important implications for our confidence in location estimates for disease genes obtained from linkage studies of modest size. In particular, collection of larger data sets and/or analysis strategies such as conditioning or narrowing the phenotype definition, in order to increase the relative effect size, may be required before embarking on positional cloning.

Alleles↗
PubMed2000

Why do females mate multiply? A review of the genetic benefits.

The aim of this review is to consider the potential benefits that females may gain from mating more than once in a single reproductive cycle. The relationship between non-genetic and genetic benefits is briefly explored. We suggest that multiple mating for purely non-genetic benefits is unlikely as it invariably leads to the possibility of genetic benefits as well. We begin by briefly reviewing the main models for genetic benefits to mate choice, and the supporting evidence that choice can increase offspring performance and the sexual attractiveness of sons. We then explain how multiple mating can elevate offspring fitness by increasing the number of potential sires that compete, when this occurs in conjunction with mechanisms of paternity biasing that function in copula or post-copulation. We begin by identifying cases where females use pre-copulatory cues to identify mates prior to remating. In the simplest case, females remate because they identify a superior mate and 'trade up' genetically. The main evidence for this process comes from extra-pair copulation in birds. Second, we note other cases where pre-copulatory cues may be less reliable and females mate with several males to promote post-copulatory mechanisms that bias paternity. Although a distinction is drawn between sperm competition and cryptic female choice, we point out that the genetic benefits to polyandry in terms of producing more viable or sexually attractive offspring do not depend on the exact mechanism that leads to biased paternity. Post-copulatory mechanisms of paternity biasing may: (1) reduce genetic incompatibility between male and female genetic contributions to offspring; (2) increase offspring viability if there is a positive correlation between traits favoured post-copulation and those that improve performance under natural selection; (3) increase the ability of sons to gain paternity when they mate with polyandrous females. A third possibility is that genetic diversity among offspring is directly favoured. This can be due to bet-hedging (due to mate assessment errors or temporal fluctuations in the environment), beneficial interactions between less related siblings or the opportunity to preferentially fertilise eggs with sperm of a specific genotype drawn from a range of stored sperm depending on prevailing environmental conditions. We use case studies from the social insects to provide some concrete examples of the role of genetic diversity among progeny in elevating fitness. We conclude that post-copulatory mechanisms provide a more reliable way of selecting a genetically compatible mate than pre-copulatory mate choice. Some of the best evidence for cryptic female choice by sperm selection is due to selection of more compatible sperm. Two future areas of research seem likely to be profitable. First, more experimental evidence is needed demonstrating that multiple mating increases offspring fitness via genetic gains. Second, the role of multiple mating in promoting assortative fertilization and increasing reproductive isolation between populations may help us to understand sympatric speciation.

Animals↗
PubMed2004

The SMILES program: a group program for children with mentally ill parents or siblings.

The Simplifying Mental Illness + Life Enhancement Skills program, for children with a mentally ill parent or sibling, is a 3-day program that aims to increase children's knowledge of mental illness and to better equip them with life skills considered beneficial for coping in their family. Self-report data from 25 children who attended 3 of these programs, in Canada and Australia, indicate that these aims were achieved. Their parents also report benefits for their children.

Adaptation, Psychological↗
PubMed2005

Sibling effects on substance use in adolescence: social contagion and genetic relatedness.

Prior research on sibling contagion for substance use has not attended to individual differences in the sibling relationship that may be influenced by genetic similarity. The authors utilizing data on a sample of twin and nontwin siblings participating in the National Longitudinal Study of Adolescent Health (Add Health). Although monozygotic twins had the highest levels of sibling contact and mutual friendships, the pattern of results for other sibling types were not consistent with genetic models, and biometric analysis indicated that shared environmental factors influenced these sibling relationship features. Application of DeFries-Fulker regression models provided evidence that sibling contact and mutual friendships represent a source of social contagion for adolescent smoking and drinking independent of genetic relatedness. The results are interpreted using a social contagion framework and contrasted with other competing models such as those focused on the equal environments assumption and niche selection.

Adolescent↗
PubMed1999

Low transplant-related mortality in patients receiving unrelated donor marrow grafts for leukemia.

Transplantation with unrelated donor (UD) marrow has been shown to potentially cure patients with leukemia. Between January 1991 and April 1998, 54 patients with leukemia have received an UD BMT at our institution. Five patients received their UD BMT as a second transplant after a preceding autologous or syngeneic BMT and were excluded from further analysis. Forty-nine patients with leukemia (acute leukemia n = 26; CML n = 23) and a median age of 36 years (range 19-51) were analyzed. For conditioning, all patients received a combination of fractionated TBI and CY. GVHD prophylaxis consisted of MTX and CsA in all patients. As of 30 April 1998, 27 of 49 (55%) patients survive after a median observation time of 18 months. The probability of overall survival for standard risk and high risk patients is 54% and 31% (P = 0.05). Probability of transplant-related mortality (TRM) is 27%, 24% in standard risk and 31% in high risk patients (P = 0.44). Patients younger than 40 years (n = 33) had a similar TRM as patients 40 years and older (n = 16). The probability of relapse is 41% for the whole group, 29% for standard risk and 55% for high risk pts (P<0.05). Our data confirm that UD BMT is an effective treatment for patients with leukemia. TRM is almost similar to related sibling BMT, most probably due to improvements in HLA typing technology, conditioning regimen and supportive patient care.

Adult↗
PubMed2000

Genetics of hand osteoarthritis.

There is convincing epidemiological evidence for a strong hereditary component to hand osteoarthritis (OA). For example: (1) greater concordance for hand OA in monozygotic than in dizygotic twins, the estimated proportion of variance explained by genetic factors being as high as 0.59; and (2) a substantially increased risk of hand OA in first-degree relatives (siblings, parents, offspring) of subjects with hand OA. Such evidence clearly justifies a search for the genes involved. However, gene association studies in genetically complex polygenic conditions such as OA present many problems, including case definition, late age of phenotype expression and adjustment for other constitutional and environmental risk factors. Nevertheless, association studies of affected sibling pairs and nuclear families, using candidate gene and genome wide screening and transmission disequilibrium testing, suggest no association with candidates such as COL2A1 (responsible for some rare monogenic syndromes of premature generalized OA) but possible associations, currently not isolated, on chromosome 2q. Such ongoing work and subsequent gene-gene and gene-environment interaction studies are likely to give important, perhaps unexpected, insights into the pathogenesis of hand OA.

Adult↗
PubMedDate not supplied

Gender role/identity and sibling sex ratio in homosexual men.

Previous research has suggested that homosexual men's sibling sex ratio-the ratio of brothers to sisters collectively reported by a group of individuals-is elevated but only in samples of extremely feminine (e.g., transsexual) homosexual men. I conducted an additional test of a sibling sex ratio effect in a general sample of homosexual men (N = 237), and examined the correlation between sibling sex ratio and childhood gender identity. I found no significant effects. My discussion focuses on why little evidence of a relationship between sibling sex ratio and cross-gender behavior in childhood occurs within this general sample of homosexual men when samples selected for very feminine homosexual men have detected an elevated sibling sex ratio.

Birth Order↗
PubMed2006

Adjustment, sibling problems and coping strategies of brothers and sisters of children with autistic spectrum disorder.

BACKGROUND: Siblings of children with autistic spectrum disorder (ASD) express more problem behaviours and experience more difficulties in their relationships than do children in families where all children are developing typically. We know little about what contributes to these difficulties. METHOD: Mothers of a child with ASD completed the Child Behavior Checklist (Achenbach, 1991) with respect to a non-disabled sibling. Siblings responded to a questionnaire tapping their knowledge about their brother or sister's disorder. They reported on problems they had experienced with their brother or sister with ASD and on the coping strategies they had used in response to these events. Problems were classified into 1 of 5 problem types. RESULTS: Aggressive behaviour was the most commonly reported interaction problem and anger was the usual response. Siblings did not generally choose blaming (either self or other) as a coping strategy when facing difficulties with their brother or sister with ASD. Neither coping strategies nor knowledge of ASD were associated with adjustment. Forty percent of non-disabled siblings had scores on the Child Behavior Checklist that placed them in the borderline or clinical range. CONCLUSIONS: The current study indicated that siblings of children with ASD are at increased risk of developing internalising behaviour problems. The contributing factors to this outcome are unknown at this point. It is important for research to focus on dynamic variables in the search for these contributors, as they are open to change.

Adaptation, Psychological↗
PubMed1998

Population-based prevalence of symptomatic and asymptomatic astrovirus infection in rural Mayan infants.

Symptomatic and asymptomatic astrovirus infection was prospectively determined in a 3-year birth cohort of Mayan infants. Stool samples from 271 infants and 268 older siblings were tested for astrovirus, adenovirus 40/41, rotavirus and Salmonella, Shigella and Campylobacter species. Concurrent diarrhea, vomiting, fever, or anorexia were noted. Astrovirus was detected in 164 infants (61%) and 20 siblings (7%). Rotavirus (4%) and adenovirus 40/41 (13%) were isolated less frequently. Of all diarrheal episodes reported at a visit, 26% (78/305) were associated with astrovirus; 17% (78/452) of astrovirus infections were associated with diarrhea and 9% with other symptoms. Only diarrhea was associated with astrovirus infection (odds ratio, 1.4; 95% confidence interval [CI], 1.07-1.92; P = .01). Of infants with astrovirus, 70% shed at multiple visits over a period of 2-17 weeks (median, 5). The point prevalence of astrovirus infection was significantly higher among infants than siblings (relative risk, 6.18; 95% CI, 3.93-9.72; P < .0001, chi2). Astrovirus was identified throughout the year, peaked in March and May, and decreased in September. In this population, astrovirus was the most common enteric pathogen isolated; symptomatic infection was prevalent among infants.

Adenoviridae Infections↗
PubMed1979

The use of restriction endonucleases to measure mitochondrial DNA sequence relatedness in natural populations. I. Population structure and evolution in the genus Peromyscus.

In this study we introduce to natural population analysis a molecular technique that involves the use of restriction endonucleases to compare mitochondrial DNA (mtDNA) sequences. We have examined the fragment patterns produced by six restriction endonucleases acting upon mtDNA isolated from 23 samples of three species of the rodent Peromyscus. Our observations confirm the following conclusions derived from previous experiments with laboratory animals: (1) mtDNA within an individual homogeneous; (2) at least the majority of mtDNA present in an individual is inherited from the female parent. Our experiments demonstrate for the first time that there is detectable heterogeneity in mtDNA sequences within and among natural geographic populations of a species and that this heterogeneity can readily be used to estimate relatedness between individuals and populations. Individuals collected within a single locale show less than 0.5% sequence divergence, while those collected from conspecific populations separated by 50 ti 500 miles differ by approximately 1.5%. The mtDNAs of the closely related sibling species P. polionotus and P. maniculatus differ from each other by 13 to 17%; nonsibling species differ by more than 20%. Qualitative and quantitative approaches to analysis of digestion patterns are suggested. The results indicate that restriction analysis of mtNDA may become the most sensitive and powerful technique yet available for reconstructing evolutionary relationships among conspecific organisms.

Animals↗
PubMed2000

Nuclear targeting determinants of the far upstream element binding protein, a c-myc transcription factor.

FUSE binding protein (FBP) binds in vivo and in vitro with the single-stranded far upstream element (FUSE) upstream of the c-myc gene. In addition to its transcriptional role, FBP and its closely related siblings FBP2 (KSRP) and FBP3 have been reported to bind RNA and participate in various steps of RNA processing, transport or catabolism. To perform these diverse functions, FBP must traffic to different nuclear sites. To identify determinants of nuclear localization, full-length FBP or fragments thereof were fused to green fluorescent protein. Fluorescent-FBP localized in the nucleus in three patterns, diffuse, dots and spots. Each pattern was conferred by a distinct nuclear localization signal (NLS): a classical bipartite NLS in the N-terminal and two non-canonical signals, an alpha-helix in the third KH-motif of the nucleic acid binding domain and a tyrosine-rich motif in the C-terminal transcription activation domain. Upon treatment with the transcription inhibitor actinomycin D, FBP completely re-localized into dots, but did not exit from the nucleus. This is in contrast to many general RNA-binding proteins, which shuttle from the nucleus upon treatment with actinomycin D. Furthermore, FBP co-localized with transcription sites and with the general transcription factor TFIIH, but not with the splicing factor SC-35. Taken together, these data reveal complex intranuclear trafficking of FBP and support a transcriptional role for this protein.

Biological Transport↗
PubMed1990

A survey of public attitudes toward oocyte donation between sisters.

Oocyte donation offers the possibility of pregnancy for many patients with premature ovarian failure (POF) and recently a number of patients have been requesting egg donation by a sister. While patients anxious to achieve a pregnancy are favourably disposed toward egg donation, the existence of favourable attitudes in others, and thus the amount of social support such patients will receive, depends upon the wider social environment. A survey of public opinion was conducted utilizing a random sample of 501 adults in Orange County, CA in an attempt to identify demographic correlates of attitudes. Log linear analysis demonstrated no relationship between attitudes and an array of demographic data (income, political party, age), but showed a significant relationship between sex of the respondent and attitudes towards egg donation. While more than half of respondents of both sexes were favourably disposed towards egg donation, men exhibited significantly (P = 0.005) more positive attitudes towards oocyte donation by a sister than did women. Women in the general population showed markedly less support for egg donation by a sister than POF patients have been demonstrated to show. The theory is proposed that female respondents are more wary of the symbolic meaning of the reproductive connection between a sister-in-law and a husband, while the POF patient's attitude is shaped in part by her desire for a pregnancy. The results have implications for the attitudes POF couples may face in the social environment and for the type of social support which may be recommended.

Directed Tissue Donation↗
PubMed2005

The inheritance of intermediate phenotypes for schizophrenia.

PURPOSE OF REVIEW: While schizophrenia is substantially heritable, the mode of inheritance is complex, involving numerous genes of small effect and a non-trivial environmental component. The 'endophenotype' approach is an alternative method for measuring phenotypic variation that may facilitate the identification of susceptibility genes in the context of complexly inherited traits. Here we review recent studies applying this method to measures of brain structure, physiology, and function in samples of schizophrenia patients and their non-ill first-degree relatives (siblings and co-twins). RECENT FINDINGS: The results suggest that there are multiple heritable dimensions of central nervous system pathology in schizophrenia, including disturbances in the structure and functioning of frontal lobe systems involved in working memory and executive processes, temporal lobe systems involved in episodic memory, auditory perception, and language processing, and cortical and sub-cortical systems mediating smooth pursuit eye movements and sensorimotor gating. A number of genetic loci that are suspected to play a role in predisposing to schizophrenia, including the DISC1, COMT, neuregulin, dysbindin, and alpha-7 nicotinic receptor genes, appear to affect quantitative variation on one or more of these indicators. SUMMARY: Future work is encouraged to address whether each of these neural system dysfunctions are under the influence of a partially distinct set of genes, to elucidate the manner in which multiple genes may coalesce in determining schizophrenia-promoting dysfunction in each neurobehavioral domain, and to clarify the degree of overlap in these quantitative trait loci-endophenotype relationships with other forms of psychosis, particularly bipolar disorder.

Journal Article↗