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PubMed2005

The recent evolution of human L1 retrotransposons.

L1 elements are the most successful retrotransposons in mammals and are responsible for at least 30% of human DNA. Far from being indolent genomic parasites, L1 elements have evolved and amplified rapidly during human evolution. Indeed during just the last 25 million years (MY) five distinct L1 families have emerged and generated tens of thousands of copies. The most recently evolved human specific L1 family is currently active and L1 copies have been accumulating in the human genome at about the same rate per generation as the currently active L1 families in Old World rats and mice. At times during the last 25 MY L1 activity constituted a significant enough genetic load to be subject to negative selection. During these same times, and in apparent response to the host, L1 underwent adaptive evolution. Understanding the molecular basis for these evolutionary changes should help illuminate one of the least understood but most important aspects of L1 biology, namely the extent and nature of the interaction between L1 and its host.

Evolution, Molecular↗
PubMed2002

Modelling the evolution of female choice strategies under inbreeding conditions.

Recently, many mate choice studies have discussed the role of genetic compatibility and inbreeding for the evolution of mate choice. With population genetic simulations I compared the potential advantage of three different female choice strategies under inbreeding conditions. Females were assumed to benefit indirectly via a preference for (i) complementary males, (ii) males with few detrimental mutations, and (iii) non-inbred males. Probably related to the reduced inbreeding depression in offspring of choosy females, the choice-allele increased for all three strategies. However, the advantage of the strategies differed widely. Choice of males with fewer mutations provided a comparatively large advantage, choice of complementary males led to a reasonable advantage, and choice of non-inbred males only resulted in a minor advantage of female choice. My results show that complementary mate choice can be almost as beneficial as conventional good-genes choice of mates with lower genetic load. Compared to the two other mate choice strategies, choice of non-inbred males is less likely to contribute to the evolution of costly mate choice. The results of a recent study showing that female sticklebacks prefer males with a larger number of MHC-loci is thus unlikely to be related to an indirect benefit of choosing non-inbred males.

Animals↗
PubMed2001

Genetic liability, illicit drug use, life stress and psychotic symptoms: preliminary findings from the Edinburgh study of people at high risk for schizophrenia.

BACKGROUND: Studies of groups at high risk of developing schizophrenia have tended to be based on subjects recruited to the study in their infancy. This paper reports on subjects at genetic high risk for schizophrenia assessed as young adults, close to the age when most onsets of schizophrenia occur. METHODS: One hundred and fifty-five young people at elevated risk for the development of schizophrenia and 36 controls not at increased risk were assessed on entry to the Edinburgh High Risk Study. The measures included current psychotic symptoms, past and present cannabis and other drug use, lifetime life events and two aspects of genetic liability to schizophrenia. RESULTS: Cannabis and other illicit drug use were significantly associated with symptoms in both groups. The same held true for the more upsetting life events experienced, but not for less upsetting ones. Within the high-risk group, there was no relationship between symptoms and a measure of genetic loading, but there was some slight evidence of a higher risk of symptoms when affected relatives were on the father's rather than the mother's side of the family. CONCLUSIONS: Cannabis use, use of other illicit substances and upsetting life events may all lead to psychotic symptoms in vulnerable young people.

Adolescent↗
PubMedDate not supplied

Electrodermal activity and vulnerability to schizophrenia: a review.

Because electrodermal variables show consistency over time and situations, and evidence of genetic loading, it is of interest to examine such measures in adult schizophrenics and in children at risk for the disorder. Samples of adult schizophrenics are heterogeneous with regard to electrodermal activity. One group, the nonresponders, fails completely to respond to simple moderate intensity nonsignal stimuli. The other, the responders, does not differ from normals in frequency of response to nonsignal stimuli, but tends to show elevated tonic levels, and bilaterally asymmetrical and rapidly recovering responses. These two groups differ in other physiological and psychological measures, and in clinical picture. The responder pattern is predictive of poor outcome of acute schizophrenic episodes. A similar hyperactive pattern was found to differentiate children genetically at high or low risk for schizophrenia, and to predict psychiatric breakdown in the former group in Mednick and Schulsinger's original high risk study. The relationship to risk has been less evident in later studies, but similar, albeit weaker, tendencies have been reported. It is concluded that the nonresponding pattern may be secondary to a clinical picture of withdrawal and confusion, whereas the responder pattern may index vulnerability to schizophrenic episodes. On the psychological level, it is argued that this relationship is best conceptualized in attentional terms couched in information-processing language.

Acoustic Stimulation↗
PubMed1988

The genetic basis of cleft lip and palate deformity.

The embryology of the normal lip and palate and the abnormal development of these structures causing cleft lip (CL) and cleft palate (CP) are discussed. As the development of the lip and palate is not dependent on a single factor but on many factors, it is understandable that CL and CP may occur as a result of abnormalities of genes of large mutant effect (i.e. Mendelian mutant genes), or due to chromosomal anomalies. However, these 2 causes are relatively uncommon and the commonest mode of production is dependent on both genetic and environmental factors. The mechanisms whereby these 3 groups may produce CL and CP will be discussed. Since the modes of inheritance differ in the 3 groups, it is important to discover which group a particular patient belongs to. The genetic load is high in the Mendelian group, is low usually in those due to chromosome disorders, and may be low or high in the last group depending on the polygenes as well as environmental factors. In this last group, empiric risk figures may be calculated for future offspring to be affected. The prenatal diagnosis of CL and CP is also discussed.

Chromosome Aberrations↗
PubMed2003

The candidate gene approach in alcoholism: are there gender-specific differences?

It is well established that genetic factors play a major role in the development of alcoholism in both sexes. Several twin studies demonstrated a nearly equally high magnitude of genetic influence for men and women. However, the genetic sources of vulnerability are supposed to only partially overlap in men and women. Therefore, we evaluated the gender-specific effects of two single nucleotide polymorphisms affecting dopaminergic neurotransmission (dopamine D2 receptor: -141C Ins/Del polymorphism; Dopamine D3 receptor: Bal I) in our large sample of primary alcoholics. Only a gender-specific analysis of subgroups with a putatively high genetic load, e.g., family-history-positive or presence of severe withdrawal complications, revealed significant differences in allele-/genotype-frequency. Our results demonstrate that a varying sex distribution in the samples investigated might contribute to the heterogeneous results reported in association studies for candidate genes in alcoholism and, therefore, should be taken into account in future studies.

Adult↗
PubMed1997

Seasonal changes in affective state in samples of Asian and white women.

Seasonality of the affective state has been reported to vary in direct proportion to latitude in temperate regions. The frequency of seasonal affective disorder (SAD) and the severity of the symptoms associated with it have been reported to be greater in higher than in lower latitudes. In addition, recent research has suggested a genetic loading for SAD. Most of the research on the seasonality of affect has been done in high latitude areas, seasonal mood cycles have been infrequently investigated in tropical areas, and no study has so far measured and compared seasonal changes in affect and behaviour in indigenous and populations non-indigenous to high latitudes. To rule out the biases associated with retrospective designs, a prospective longitudinal study was designed to investigate seasonal mood variations in indigenous white and non-indigenous Asian populations. Since previous research has indicated the excessive vulnerability of women to winter depression, it was decided to measure seasonality of the affective state only in women. To examine the relative effects of genetic predispositions and physical environment, the Asian group was further divided into "Asian" and "Asian-British". The former group comprised women who were living in England but who had been born and had spent considerably more time in their country of origin, while the latter group consisted of women who were born in England and who had lived there all their lives. The three groups of 25 women each were matched for age and socio-economic status, and were interviewed every month for 1 year using the Hospital Anxiety and Depression Scale (HAD), a Behavioural Change Inventory (BCI), the Ladder Scale of General Well-being (LSW) and a Monthly Stress Inventory (MSI). One retrospective scale was administered at the end of the study year to compare the extent of seasonal change in affect with that on the HAD-depression subscale. The results showed that seasonal depression peaked in winter in all three groups, with the incidence of winter depression being highest in the Asian group. Seasonal changes on several dimensions of behaviour were in the direction of winter depression for all three groups. States other than depression (anxiety and general well-being) did not show any seasonal variation. Hours of daylight was found to be the best predictor of seasonal variation in mood among environmental and psychosocial variables. There was no evidence to support a genetic hypothesis for SAD.

Adult↗
PubMed2005

Predictors of schizophrenia--a review.

Schizophrenia is an aetiologically heterogeneous syndrome that usually becomes overtly manifest in adolescence and early adulthood, but in many cases subtle impairments in neurointegrative function are present from birth; hence it is considered to be a disorder with a neurodevelopmental component. The strongest risk factor that has been identified is familial risk with genetic loading. Other risk factors include pregnancy and delivery complications, infections during pregnancy, disturbances of early neuromotor and cognitive development and heavy cannabis use in adolescence. Unfortunately, to date it has not been possible to utilize the predictors of the disorder that have been identified in primary preventative interventions in a general population. However, some authors have claimed that in future it might be possible to reduce the risk for developing schizophrenia through general health policy. In clinical settings, it is helpful to map out possible early risk factors, at least familial risk for psychosis, especially in child, adolescent and young adult mental patients. Furthermore, in the future we may have predictive models combining data from genetic factors for schizophrenia, antenatal risk factors, childhood and adolescent development and clinical symptomatology, as well as brain structural and functional abnormalities.

Adolescent↗
PubMed1986

Parkinson's disease: a genetic study.

A sample of 122 patients with Parkinson's Disease was studied for the purpose of investigating if the frequency of relatives affected with Parkinson in this group was higher than in a control group and to see if the genetic load was more important in some of the subtypes of Parkinson described by Barbeau and Pourcher (1982). In our 122 patients, we found that 1.7% were post-encephalic parkinsonian, 12.3% were symptomatic cases and 86% of the idiopathic variety. There were 16.1% early onset patients in the idiopathic group and among these we found 23.5% with a positive family history of Parkinson in the first-degree relatives. In 6 cases with the tremor onset form of the disease, the family history was positive and 5 patients, 4.7% had familial essential tremor-related Parkinsonism. Our results support Barbeau's hypothesis that Parkinson is a heterogeneous disease in which some subtypes (such as early onset Parkinson) have an important genetic susceptibility component.

Female↗
PubMed2002

The temporal lobe in schizophrenia from uni- and multiply affected families.

To investigate the effect of genetic loading on brain structure in schizophrenia, we hypothesized that separating families into uniaffected and multiply affected would reveal effects of schizophrenia and family type. Volumes and asymmetries of the amygdala-hippocampus-complex (AHC) and sylvian fissure (SF) were determined using magnetic resonance imaging of subjects with schizophrenia from 12 uniaffected and 14 multiply affected families, and ten healthy controls. AHC volume was reduced in schizophrenia, particularly on the right side in subjects from uniaffected families. AHC asymmetry was disturbed, too. Enlargement of the right SF and disturbed SF asymmetry was demonstrated in subjects from uniaffected families as well. Comparing subjects from uni- and multiply affected families may be a useful strategy to reduce variability for future studies of environmental interactions with genetic risk for schizophrenia.

Adult↗
PubMed1998

Risk factors for mortality in young children living under various socio-economic conditions in Lahore, Pakistan: with particular reference to inbreeding.

Risk factors such as maternal age, parity, previous siblings' death, inbreeding of parents, birth weight, birth length were examined in a population-based prospective study in four population groups at different levels of urbanization in and round Lahore, Pakistan. From September 1984 to March 1995, 2967 full-term, single born infants were followed from the 5th month of gestation to 12 months of age. Logistic regression analysis showed a significant relative risk (RR) of infant death associated with parents' consanguinity (RR = 1.8), birth weight (RR = 1.8) and elder siblings' death (RR = 1.7). The risk attributed to these factors was 28, 17 and 25%, respectively. The number of lethal equivalents per gamete is about one. The B/A ratio 10.36 suggests that the genetic load is likely to be mutational. In countries like Pakistan, where consanguinity is favourably practiced, a substantial proportion of infant deaths may be prevented by cessation of such marriages. The implications of this finding for the Pakistani community are discussed.

Adolescent↗
PubMed2000

Inbreeding depression due to mildly deleterious mutations in finite populations: size does matter.

We studied the effects of population size on the inbreeding depression and genetic load caused by deleterious mutations at a single locus. Analysis shows how the inbreeding depression decreases as population size becomes smaller and/or the rate of inbreeding increases. This pattern contrasts with that for the load, which increases as population size becomes smaller but decreases as inbreeding rate goes up. The depression and load both approach asymptotic limits when the population size becomes very large or very small. Numerical results show that the transition between the small and the large population regimes is quite rapid, and occurs largely over a range of population sizes that vary by a factor of 10. The effects of drift on inbreeding depression may bias some estimates of the genomic rate of deleterious mutation. These effects could also be important in the evolution of breeding systems in hermaphroditic organisms and in the conservation of endangered populations.

Genetics, Population↗
PubMed2001

Inflammatory eye, skin, and bowel disease in spondyloarthritis: genetic, phenotypic, and environmental factors.

OBJECTIVE: To explore the nature of the interrelationship between inflammatory disease of the spine/joints, skin, eye, and bowel [i.e., ankylosing spondylitis (AS), psoriasis, iritis, inflammatory bowel disease (IBD)]. METHODS: The study used 4 approaches: (1) analysis of the prevalence of secondary disorders within the AS individual (chi-square and matched pair analysis); (2) study of the temporal relationship between the onset of the different conditions; (3) evaluation of the prevalence of disease among first degree relatives; and (4) influence of secondary disorders on outcome of AS. RESULTS: 1. Among 3287 patients with AS, more than expected had either spondylitis associated with multiple co-disorders or pure AS (with no co-diseases); fewer than expected had AS plus a single co-disease (chi-square = 32.2, p < 0.001). In a matched pair analysis, patients with AS and a secondary disorder were more likely to have an additional concomitant disease, e.g., IBD-AS (n = 335) patients had a higher prevalence of iritis [45.4% vs 36.7%; OR 1.4 (1.1-2.0)] or psoriasis [23.9% vs 14.3%; OR 1.9 (1.3-2.8)] than controls. 2. Among our database subjects, the symptomatic onset of the spinal disease precedes or is contemporaneous with gut, skin, and eye involvement (matched pair t test, p < 0.001). 3. Patients with multiple disorders predict the highest prevalence of co-diseases (i.e., psoriasis, IBD, iritis, or AS) within family members, followed by those AS patients with only IBD, psoriasis, or iritis in descending order. 4. Both psoriasis and IBD increase severity in terrms of function and disease activity of AS in the patient. Radiological change is greatest for those AS subjects with iritis. CONCLUSION: There is a striking overlap within patients and family members of rheumatological, dermatological, and gastroenterological diseases. The susceptibility genes of these co-disorders appear to overlap with each other and with AS: 1. A patient with 2 inflammatory conditions is at an increased risk of developing an additional related inflammatory disorder. 2. Those with enteropathic spondylarthritis would appear to carry the greatest genetic load in terms of first degree relatives developing inflammatory conditions (including psoriasis and iritis that are not seen in the index IBD-AS patient). 3. The secondary disorders do not precede AS (arguing against psoriasis and IBD allowing for an environmental conduit to pathogenic triggers in AS). The susceptibility factors for these inflammatory conditions may be additive or have a synergistic effect on each other. There is evidence for a shared gene hypothesis.

Age of Onset↗
PubMed1994

Genetic factors in substance abuse based on studies of Tourette syndrome and ADHD probands and relatives. II. Alcohol abuse.

Prior studies have suggested childhood attention deficit hyperactivity disorder (ADHD) as a risk factor for alcohol abuse in adults. Gilles de la Tourette Syndrome, a hereditary tic and impulse disorder, is clinically and genetically similar to ADHD. To examine the hypothesis that individuals carrying the Gts gene are at increased risk to develop alcohol use problems, the same TS (Tourette Syndrome) and ADHD probands, relatives and controls used in the prior study of drug abuse were also studied using a structured questionnaire based on the Diagnostic Interview Schedule and the MAST test. The frequency of a positive response to any of 16 different questions concerning alcohol abuse showed a highly significant increase with increased genetic loading for Gts and ADHD genes. The percentage of more than one positive response in TS probands was markedly influenced by the presence of comorbid ADHD, discipline, obsessive-compulsive or drug abuse problems. Comorbid drug abuse problems were the best predictor of alcohol abuse problems. These results suggest that the genes responsible for TS and ADHD play an important role in alcohol abuse/dependence as well as drug abuse/dependence. One of the elements common to all of these disorders may be mutant genes affecting serotonin metabolism.

Adolescent↗
PubMed2002

GJB2 mutations in Iranians with autosomal recessive non-syndromic sensorineural hearing loss.

Hereditary hearing loss (HHL) is an extremely common disorder. About 70% of HHL is non-syndromic, with autosomal recessive forms accounting for approximately 85% of the genetic load. Although very heterogeneous, the most common cause of HHL in many different world populations is mutations of GJB2, a gene that encodes the gap junction protein connexin 26 (Cx26). This study investigates the contribution of GJB2 to the autosomal recessive non-syndromic deafness (ARNSD) load in the Iranian population. One hundred sixty eight persons from 83 families were studied. GJB2-related deafness was diagnosed in 9 families (4, 35delG homozygotes; 3, 35delG compound heterozygotes; 1, W24X homozygote; 1, non-35delG compound heterozygote). The carrier frequency of the 35delG allele in this population was approximately 1% (1/83). Because the relative frequency of Cx26 mutations is much less than in the other populations, it is possible that mutations in other genes play a major role in ARNSD in Iran.

Connexin 26↗
PubMed2025

Evolutionary Genomics Unravels the Responses and Adaptation to Climate Change in a Key Alpine Forest Tree Species.

Despite widespread biodiversity loss, our understanding of how species and populations will respond to accelerated climate change remains limited. In this study, we integrate population genomics, experimental evolution, and environmental modeling to elucidate the evolutionary responses to climate change in Populus lasiocarpa, a key alpine forest tree species primarily distributed in the mountainous regions of a global biodiversity hotspot. Over historical timescales, our findings demonstrate that demographic dynamics, divergent selection, and long-term balancing selection have shaped and maintained genetic variation within and between populations. In examining genomic signatures of contemporary climate adaptation, we found that haplotype blocks, potentially caused by inversion polymorphisms that suppress recombination, are linked to enriched combinations of locally adaptive environmental variations. We further assessed the relative contributions of environmentally induced plastic responses, constitutive expression divergence between genetic clusters, and their interactions in driving gene expression variation and divergence. Notably, we observed a strong correlation between sequence divergence and constitutive differential expression among genetic clusters. Finally, by incorporating genetic adaptation, migration, and genetic load into our predictions of population-level climate change risks, we identified western populations-primarily distributed in the Hengduan Mountains, a region known for its environmental heterogeneity and significant biodiversity-as the most vulnerable to climate change. These populations should be prioritized for conservation and management. Overall, our study advances the understanding of the relative roles of long-term natural selection, local environmental adaptation, and immediate plastic expression changes in shaping the responses of natural populations of keystone species to climate change.

Climate Change↗
PubMed1993

Effect of a founder event on variation in the genetic sex-determining system of the fire ant Solenopsis invicta.

Effects of a recent founder event on genetic diversity in wild populations of the fire ant Solenopsis invicta were studied, with particular attention given to the genetic sex-determining system. Diploid males are far more common relative to haploid males in introduced populations than in native populations of fire ants, and queens that produce diploid males account for a significantly larger proportion of the mated queens in introduced than in native populations. Differences between native and introduced populations in attributes of the mating systems (i.e., queen mating frequency or level of inbreeding) can be excluded as factors contributing to these different levels of diploid male production. Thus, we conclude that diploid males have increased in frequency in introduced populations because of a loss of allelic diversity at the sex-determining locus (loci). This loss of sex alleles has generated a substantial increase in the estimated segregational genetic load associated with production of sterile diploid males in introduced populations over the load in native populations. The loss of allelic diversity in the sex-determining system in introduced S. invicta is paralleled by a loss of electrophoretically detectable rare alleles at protein-encoding loci. Such concordance between these different types of markers is predicted because each of the many sex alleles present in the native populations is expected to be rare. Estimates of expected heterozygosity (Hexp) based on 76 electrophoretic loci do not differ significantly between the native and introduced fire ant populations, illustrating the lack of sensitivity of this measure for detecting many types of bottlenecks.

Alleles↗
PubMed1972

Viabilities of third chromosomes of Drosophila pseudoobscura differing in relative competitive fitness.

Arrowhead (AR) third chromosome arrangements of Drosophila pseudoobscura, whose competitive fitnesses had been determined in population cages, were tested for their genetic loads in homozygous, heterozygous (homokaryotypic), and heterokaryotypic (AR/CH) combinations. The results showed that their competitive population cage performances were correlated to their viabilities as homozygotes but were not correlated to their viabilities as heterozygotes or as heterokaryotypes. However, the results do not fit in too simply with the mutational model of population structure, since the improvement of homozygous viability with increased competitive fitness was not accompanied by a significant degree of dominance as measured by the regression of viabilities of heterozygotes on homozygotes. Only the AR chromosomes derived from the population with poorest competitive fitness showed marked partial dominance (h=.35). The viabilities of heterokaryotypes were markedly uniform for all chromosomes tested and produced significantly greater numbers of flies per culture than the homokaryotypes. In general, the results show that the ranking of relative competitive fitnesses of these chromosomes is not a simple extrapolation of their viabilities, although marked changes in the populations tested have occurred. It is proposed that the differences in competitive fitness, homozygous viability, and degree of dominance observed among these chromosomes, arise from differences in genetic variability which enable different linkage relationships to be established for genes affecting these attributes.

Animals↗