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Results for “Genetic Pleiotropy”

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PubMed2005

Mitochondrial genetic effects on latent class variables associated with susceptibility to alcoholism.

We report the results of statistical genetic analyses of data from the Collaborative Study on the Genetics of Alcoholism prepared for the Genetic Analysis Workshop 14 to detect and characterize maternally inherited mitochondrial genetic effects on variation in latent class psychiatric/behavioral variables employed in the diagnosis of alcoholism. Using published extensions to variance decomposition methods for statistical genetic analysis of continuous and discrete traits we: 1) estimated the proportion of the variance in each trait due to the effects of mitochondrial DNA (mtDNA), 2) tested for pleiotropy, both mitochondrial genetic and residual additive genetic, between trait pairs, and 3) evaluated whether the simultaneous estimation of mitochondrial genetic effects on these traits improves our ability to detect and localize quantitative trait loci (QTL) in the nuclear genome. After correction for multiple testing, we find significant (p < 0.009) mitochondrial genetic contributions to the variance for two latent class variables. Although we do detect significant residual additive genetic correlations between the two traits, there is no evidence of a residual mitochondrial genetic correlation between them. Evidence for autosomal QTL for these traits is improved when linkage screens are conditioned on significant mitochondrial genetic effects. We conclude that mitochondrial genes may contribute to variation in some latent class psychiatric/behavioral variables associated with alcoholism.

Alcoholism↗

PubMed2006

Generalist genes: implications for the cognitive sciences.

In the 'generalist genes' hypothesis, it is suggested that the same genes affect most cognitive abilities and disabilities. This recently proposed hypothesis is based on considerable multivariate genetic research showing that there is substantial genetic overlap between such broad areas of cognition as language, reading, mathematics and general cognitive ability. We assume that the hypothesis is correct and consider here its implications for cognitive neuroscience. In our opinion, the two key genetic concepts of pleiotropy (in which one gene affects many traits) and polygenicity (in which many genes affect a trait) that underlie the generalist genes hypothesis imply a 'generalist brain'. That is, the genetic input into brain structure and function is general not specific.

Animals↗

PubMed1990

Usher's syndrome.

Usher's syndrome is an autosomal recessive condition of congenital sensorineural hearing loss and retinitis pigmentosa. Other abnormalities are present but inconsistently, suggesting the genetic concepts of pleiotropy and heterogeneity. Accordingly, several classifications have been suggested. Clinical findings involve the visual, auditory and vestibular systems. The identification of the carrier state would allow for more timely and accurate genetic counselling. A screening program for Usher's syndrome appears feasible. This would allow affected, deaf individuals to prepare themselves for the expected visual loss giving them a better chance for a productive, fulfilling life.

Genetic Counseling↗

PubMed1997

Sex and death in the mouse: genetically delayed reproduction and senescence.

A mammalian model of genetically postponed aging would be an important tool to test not only different mechanisms of aging but also the predictive value of various biomarkers of the aging process. Under conventional conditions, the historical strains of the laboratory mouse produce their first litter between 9 and 13 weeks of age and have a median time of death in their 2nd year. Our POSCH-2 strain, which was derived from wild-caught Mus musculus domesticus, produces its first litter in the current breeding generations at approximately 47 weeks of age and continues to breed throughout its 2nd and into its 3rd year of life. The aging curve of POSCH-2 has not yet been determined for economic reasons. Late onset of breeding is a characteristic of both females and males, but sexual maturity is more reliably assessed in females. The later breeding phenotype of POSCH-2 is genetically recessive to early breeding of the C57BL/6J historical laboratory strain and, since POSCH-2 females can be induced to ovulate at 8 weeks of age (but pregnancy does not result), the signal rather than the ovarian receptor to ovulate may be delayed. The genetically delayed reproduction and potentially longer life of the POSCH-2 strain appears to be a new trait in the mouse. The strain may be a useful mammalian model for aging studies and for the evaluation of antagonistic pleiotropy as a genetic model for the evolution of aging.

Aging↗

PubMed1997

Genetic relationship between measures of HDL phenotypes and insulin concentrations.

We used data from the San Antonio Family Heart Study to determine the HDL correlates of the insulin resistance syndrome (IRS), as reflected by insulin concentrations in nondiabetic subjects. We measured insulin concentrations both in the fasting state and 2 hours after a glucose challenge (2-hour insulin) and we assessed seven aspects of HDL phenotype, including size and concentration of both lipid and protein components. Measurements were obtained from 1202 nondiabetic members of 42 families. Initial quantitative genetic analyses revealed that a substantial portion of phenotypic variation in the nine variables was due to genes (heritabilities, h2, ranged from 0.32 to 0.47). We then conducted a series of bivariate genetic analyses, which indicated that there were significant additive genetic correlations (ie, pleiotropy) between the two measures of insulin and five of seven HDL measures tested, including concentrations of HDL cholesterol (fasting insulin only) and triglyceride, and HDL size distributions of apoAI, apoAII, and cholesterol; concentrations of apoAI and apoAII were not genetically related to either insulin measure. Increased insulin levels were associated with relatively smaller HDL phenotypes, and considering a similar association with small, dense LDLs, this finding suggests a common effect of insulin resistance on particle size distributions for these lipoproteins. Thus, these results suggest the existence of genes that pleiotropically influence variation in both HDLs and insulin levels and therefore contribute to the clustering of proatherogenic traits in the IRS.

Adult↗

PubMed2006

Antagonistic pleiotropy may help population-level selection in maintaining genetic polymorphism for transmission rate in a model phytopathogenic fungus.

It has been shown theoretically that the conditions for the maintenance of polymorphism at pleiotropic loci with antagonistic effects on fitness components are rather restrictive. Here, we use a metapopulation model to investigate whether antagonistic pleiotropy could help maintain polymorphism involving common deleterious alleles in the phytopathogenic fungus Microbotryum violaceum. This fungus causes anther smut disease of the Caryophyllaceae. A previous model has shown that the sex-linked deleterious alleles can be maintained under a metapopulation structure, when intra-tetrad selfing (mating between products of the same meiosis) is high, due to founder effects and selection at the population level. Here, we add two types of pleiotropic advantages to the metapopulation model. A competitive advantage for strains carrying the sex-linked deleterious alleles did not facilitate their maintenance because competitive situations were too rare. In contrast, higher spore production did facilitate the maintenance of the deleterious alleles at low intra-tetrad mating rates and with a large advantage for spore production. These results show that antagonistic pleiotropy may promote the persistence of genetic variation, in combination with other selective forces.

Basidiomycota↗

PubMed1986

Genetic determination of striatal tyrosine hydroxylase activity in mice.

An additive major gene effect is described for tyrosine hydroxylase activity in mouse corpus striatum (CS). Quantitative genetic analysis indicated the presence of a segregating Mendelian factor with robust additive effect in F2 generations derived from crossing two highly inbred mouse strains, C57BL/6ByJ and BALB/cJ, with intermediate (INT) and high (HI) TH activity in CS. Significant positive correlation was found between striatal and mesencephalic TH activity in the segregating generations, raising the possibility that a common single gene may express its effect through pleiotropy or linkage. Genetic preparations taking advantage of the major gene effect should serve well as animal models of DA-mediated neuropsychiatric disorders.

Animals↗

PubMedDate not supplied

Genetic basis of adaptive shape differences in the cichlid head.

East African cichlids exhibit an extraordinary level of morphological diversity. Key to their success has been a dramatic radiation in trophic biology, which has occurred rapidly and repeatedly in different lakes. In this report we take the first step in understanding the genetic basis of differences in cichlid oral jaw design. We estimate the effective number of genetic factors that control differences in the cichlid head through a comprehensive morphological assessment of two Lake Malawi cichlid species and their F(1) and F(2) hybrid progeny. We estimate that between one and 11 factors underlie shape difference of individual bony elements. We show that many of the skeletal differences in the head and oral jaw apparatus are inherited together, suggesting a degree of pleiotropy in the genetic architecture of this character complex. Moreover, we find that cosegregation of shape differences in different elements corresponds to developmental, rather than functional, units.

Adaptation, Physiological↗

PubMed1975

"Spontaneously" hypertensive mice: a potential genetic model for the study of the relationship between heart size and blood pressure.

Mice selected genetically for high and low blood pressure (BP) were compared with regard to heart weight and heart/body ratios. Two experiments were performed with mice ranging in age from 1.3 to 9 months and 11 to 23 months respectively. In a third experiment C57BL/6J mice were compared to the high and low BP mice. Heart/body ratios and heart weights, adjusted fo body weight via covariance analysis, were significantly greater for the high BP mice, but no Age x BP Genotype interaction was observed. Results were discussed in terms of a possible relationship between heart weight and BP via genetic linkage or pleiotropy. The possibility was also raised that compensatory mechanisms for high blood pressure, e.g., cardiac hypertrophy, may operate very early in development for animals who are hypertensive by virtue of selective breeding for blood pressure extremes.

Age Factors↗

PubMed2002

Molecular dissection of the genetic relationships of source, sink and transport tissue with yield traits in rice.

Source, sink, and translocation capacity of assimilates play important roles during the formation of grain yield. The present study was conducted to characterize the genetic bases of traits representing source, sink and transport tissue, and their relationships with yield traits in rice, by analyzing QTLs for these traits and various ratios among them. The genetic materials were a recombinant inbred population derived from a cross between two indica cultivars Zhenshan 97 and Minghui 63, the parents of the most-widely grown hybrid rice in China. Using a linkage map that covers a total of 1,796 cM based on 221 molecular marker loci, a total of 81 QTLs were identified for the 15 traits studied (three leaf areas as the source, total spikelets per panicle as the sink, the number of large vascular bundles in the stem as transport tissue, three source to sink ratios, three transport tissue to source ratios, one transport tissue to sink ratio and three yield traits). The amount of variation explained by individual QTLs ranged from 1.12% to 24.14%. Five QTLs were identified to show interaction effects with the environment, which explained from 3.19% to 9.15% of the variation. The results showed that close linkage or pleiotropy is the genetic basis for the correlations of grain yield traits with source, sink, transport tissue and the various ratios among them. Of the 25 QTLs identified for source-sink-transport tissue trait, and 43 for various ratios, 8 and 22 QTLs, respectively, were mapped to the similar genomic blocks harboring QTLs for yield traits, especially for grain weight. Co-location of QTLs for yield traits with those for ratios among source, sink and transport tissue may provide a genetic explanation for the physiological expression of yield traits, and also suggest that improvement in ratios among source, sink and transport tissue may result in improvement in yield potential.

Chimera↗

PubMed2006

Innate nonhost immunity in barley to different heterologous rust fungi is controlled by sets of resistance genes with different and overlapping specificities.

We developed an evolutionary relevant model system, barley-Puccinia [corrected] rust fungi, to study the inheritance and specificity of plant factors that determine to what extent innate nonhost immunity can be suppressed. A mapping population was developed from a cross between an experimental barley line (SusPtrit) [corrected] with exceptional susceptibility to several heterologous [corrected] (nonhost) rust fungi and regular, immune, cv. Vada [corrected] Seedlings were inoculated with five heterologous [corrected] and two homologous (host) species of rust fungi. Resistance segregated quantitatively for each of the rust fungi. In total, 18 chromosomal regions were implicated. For each rust species, a different set of genes was effective. Of the 18 chromosomal regions, 11 were significantly effective to only one rust species and 7 were effective to more than one rust species, implying genetic linkage or pleiotropy. One resistance (R) gene for hypersensitive resistance to Puccinia hordei-secalini was mapped, suggesting occasional contribution of R genes to nonhost resistance in barley. Quantitative trait loci (QTLs) with effects to multiple rust fungi did not tend to be particularly effective to rust species that were phylogenetically related, as determined from their internal transcribed spacer sequence. We suggest that the QTLs described here play a role as specific and quantitative recognition factors that are specifically negated by the rust to successfully suppress innate immunity.

Basidiomycota↗

PubMedDate not supplied

Seckel-like syndrome in three siblings.

Seckel syndrome has been described as the prototype of the primordial bird-headed type of dwarfism. Since Seckel originally defined the disorder, less than 60 cases have been reported. In addition to the characteristic craniofacial dysmorphism and skeletal defects, abnormalities have been described in the cardiovascular, hematopoietic, endocrine, and central nervous systems. This pleiotropy has implied genetic heterogeneity and prompted reviews of previously reported cases of Seckel syndrome. As a result, the characteristic diagnostic features of Seckel syndrome have been highly debated. Although deletions in chromosome 2q have been described, to date, no genetic defect has been defined. We report three cases of Seckel-like syndrome in siblings from nonconsanguinous Caucasian parents. In addition to the typical Seckel phenotypic features, all three cases were characterized by severe hydrocephalus. We review the literature and propose that there is a spectrum of Seckel conditions that share some common key features, but also demonstrate a wide range of phenotypic features.

Abnormalities, Multiple↗

PubMedDate not supplied

Mapping a cave fish genome: polygenic systems and regressive evolution.

We used random amplified polymorphic DNA (RAPD) fingerprinting to generate anonymous DNA markers in the fish Astyanax mexicanus, a species with both surface and cave populations. Surface individuals are eyed and pigmented; troglobitic forms are blind and depigmented. We hybridized surface fish and Pachon population cave fish and produced a RAPD genomic map 1064 cM in length (about half the total length of the genome) that was used to screen for quantitative trait loci (QTL) for troglomorphic traits. Three QTL for reduced eye size, two for decreased numbers of melanophores, two for condition factor, and the locus for the unifactorial trait, albinism, were mapped. These factors account for an average of 46% of the variance in these traits in the backcross. The results are the first direct demonstration that troglomorphic changes in this population are multifactorial. Two closely linked pairs of QTL were found. Each consisted of a regressive and a constructive trait QTL. These close linkages are unlikely to have occurred by chance (P <.05 for each) and suggest that troglomorphic evolution might be facilitated by pleiotropy or by genetic hitchhiking.

Animals↗

PubMed2006

Uveal coloboma: clinical and basic science update.

PURPOSE OF REVIEW: To integrate knowledge on the embryologic and molecular basis of optic fissure closure with clinical observations in patients with uveal coloboma. RECENT FINDINGS: Closure of the optic fissure has been well characterized and many genetic alterations have been associated with coloboma; however, molecular mechanisms leading to coloboma remain largely unknown. In the past decade, we have gained better understanding of genes critical to eye development; however, mutations in these genes have been found in few individuals with coloboma. CHD7 mutations have been identified in patients with CHARGE syndrome (coloboma, heart defects, choanal atresia, retarded growth, genital anomalies, and ear anomalies or deafness). Animal models are bringing us closer to a molecular understanding of optic fissure closure. SUMMARY: Optic fissure closure requires precise orchestration in timing and apposition of two poles of the optic cup. The relative roles of genetics and environment on this process remain elusive. While most cases of coloboma are sporadic, autosomal dominant, autosomal recessive, and X-linked inheritance patterns have been described. Genetically, colobomata demonstrate pleiotropy, heterogeneity, variable expressivity, and reduced penetrance. Coloboma is a complex disorder with a variable prognosis and requires regular examination to optimize visual acuity and to monitor for potential complications.

Blindness↗

PubMed1997

Models of selective mating and the initiation of the Fisherian process.

The effects of various rules of selective mating on the initial stages of Fisherian sexual selection are investigated. A comparison of three models of selective mating, fixed relative preference, best of N males and absolute preference is provided, with a special emphasis on their mathematical properties. Using a two-locus haploid model of sexual selection in a polygamous population, I show that the absolute preference rule of selective mating may lower the threshold frequency of the preference trait, required for the initiation of the Fisherian process, as low as zero. This was not observed in the previous analyses with fixed relative preference or best of N male rules. It is then argued that absolute preference may cause the initiations of the Fisherian process more easily without introducing additional assumptions such as pleiotropy or random genetic drift. Some problems associated with the mating rule are also discussed.

Animals↗

PubMed2003

Pleiotropic effects on cardiovascular risk factors within and between the fourth and sixth decades of life: implications for genotype x age interactions.

We used an approach for detecting genotype x environment interactions to detect and characterize genotype x age interaction in longitudinal measures of three well known cardiovascular risk factors: total plasma cholesterol (TC), systolic blood pressure (SBP), and body weight (Wgt). Our objectives were to determine if the same gene or suite of genes influences quantitative variation in each of these phenotypes in the 4th and 6th decades of life, to assess the impact of additive gene effects in these two decades, and to evaluate the stability of pleiotropic relationships among these phenotypes. Using the Framingham Heart Study data, we constructed two cross-sectional samples comprising individuals on whom these phenotypes were measured at ages 30-39 years (Original Cohort: exam 1, Offspring Cohort: exam 2) and at ages 50-59 years (Original Cohort: exam 11, Offspring Cohort: exam 5). We also constructed a longitudinal sample from the cross-sectional sample members for whom measures on these traits were available at both ages (i.e., 4th and 6th decades of life). Patterns of pleiotropy, inferred from genetic correlations between traits, differ between the two age classes. Further, additive genetic variance in SBP during the 4th decade of life is attributable to a different gene or suite of genes than during the 6th. The magnitude of the effect increases for SBP. Variation in TC and Wgt appear to be influenced by the same gene or genes in both decades. The magnitude of the effect is stable for TC, but increases dramatically with age for Wgt.

Adult↗

PubMed1989

Concordant deletions of chromosome 3p and loss of heterozygosity for chromosomes 13 and 17 in small cell lung carcinoma.

Common regions of loss of heterozygosity on chromosomes 3, 13, and 17 were determined by restriction fragment length polymorphism analysis in 34 tumors and nine cell lines from 27 patients with small cell lung carcinoma. The common regions of loss of heterozygosity on chromosomes 3, 13, and 17 reside between D3S2 (3p14-p21) and ERBA beta (3p22-p24.1), between D13S1 (13q12) and D13S2 (13q22), and distal to MYH2 (17p13.1), respectively. Allele loss in each of these regions has been previously shown in several human tumors. Thus, the present findings indicate the pleiotropy of recessive genetic lesions in these genomic areas. Cytogenetic analysis was performed on three small cell lung carcinoma cell lines which had allele loss on all three chromosomes, and although chromosome 3p deletions were observed in two of three cell lines, no obvious structural abnormalities involving chromosomes 13 and 17 were detected. Mitotic recombination or mitotic nondisjunction rather than deletion may thus be the frequent chromosomal mechanism for attaining homozygosity of chromosomes 13 and 17 in small cell lung carcinoma.

Alleles↗

PubMed2025

Saturating the eQTL map in Drosophila: Genome-wide patterns of cis and trans regulation of transcriptional variation in outbred populations.

Most genetic polymorphisms associated with complex traits are found in non-coding regions of the genome. Characterizing their effect presents a formidable challenge, and expression quantitative trait locus (eQTLs) mapping has been a key approach to do so. As comprehensive eQTL maps are available only for a few species, here we developed the Drosophila outbred synthetic population (Dros-OSP) and used it to characterize the landscape of transcriptional regulation in Drosophila melanogaster. We collected head and body transcriptomes and genomes from 1,286 outbred flies and mapped local and distant eQTLs for 98% of the genes. We characterized the network organization of the transcriptome across tissues and described the properties of local and distal eQTLs in terms of genetic diversity, heritability, connectivity, and pleiotropy. These results provide new insights into the genetic basis of transcriptional regulation in the fruit fly and offer a new mapping resource that will expand the possibilities currently available for the Drosophila community.

Animals↗