PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Genetic correlation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1994

Selection on reaction norms, genetic correlations and constraints.

Two approaches to the evolution of phenotypic plasticity in heterogeneous environments have recently been put forward. The first focuses on selection on the character expression within each environment; plasticity is seen as a by-product of local selection in various habitats. The second approach focuses on selection on the parameters of the response function of genotypes, and selection is thought to change the frequencies of 'plasticity' genes that affect the function. This paper discusses the relationship between the two approaches, with emphasis on applications. A method is described that allows switching from one approach to the other. It is argued that character state and reaction norm approaches, while to a large extent interchangeable, usually differ in the response function chosen. This choice, however, may strongly affect the biological interpretation. The methods outlined in this paper permit one to look at the data from different perspectives in order to avoid this danger.

Animals↗
PubMed1995

[Fragile X syndrome: clinical and molecular genetics correlations].

The fragile X form of mental retardation is presently recognized as the most frequent hereditable cause of mental impairment. The estimated frequency among males is 1 in 1250, and 1 in 2000 among females. Beside mental impairment and behavioural disturbance with hyperactivity and autistic features, the patients are characterized by morphological anomalies, such as an oblong face, broad, rectangular chin, large protruding ears and macro-orchidism. A less severe clinical expression can be found among females heterozygotes of the disorder, manifesting mainly as learning disability. The disorder is associated with the expression of a fragile site at Xq27.3 under conditions of folate depletion in the chromosome culture medium. The molecular mechanism is based on the expansion of a trinucleotide repeat [CCG]n in the promoter region of the FMR1 gene resulting in methylation of the gene. The trinucleotide repeat shows variable lengths of 6 to 53 repeats in the general population, 60 to 200 repeats in carriers of a premutation and over 200 repeats in patients with fragile X syndrome.

Adult↗
PubMed2006

Genetic correlates in trichotillomania--A case-control association study in the South African Caucasian population.

BACKGROUND: Trichotillomania (TTM), a prevalent and disabling psychiatric disorder characterized by repetitive hair-pulling, is presently classified as an impulse control disorder (ICD). Some have argued, however, that TTM is an obsessive-compulsive spectrum disorder (OCSD). There is some evidence that both disorders (OCD and TTM) are mediated by serotonergic (5-HT) and dopaminergic pathways. METHODS: The aim of the present investigation was to assess the role of candidate genes encoding components within the 5-HT and dopaminergic neurotransmitter pathways in mediating TTM. South African Caucasian TTM subjects (n=39), OCD (n=250) and control subjects (n=152) were genotyped for variants in 5-HT and dopaminergic candidate genes. RESULTS: Both genotypic and allelic distributions of the 5-HT receptor 2A (5-HT2A) T102C variant were found to be significantly different between the TTM and control subjects (p=0.028 and p=0.024, respectively), and a trend towards significance was noted between the TTM and OCD subjects (p=0.084 and p=0.080 for genotype and allele analyses, respectively), with the T102T-genotype found to confer susceptibility to the development of TTM. CONCLUSION: This investigation provides preliminary evidence for the involvement of 5-HT2A in the molecular aetiology of TTM and supports the need for further replication in a larger dataset. The present data are consistent with previous findings that 5-HT2A plays a role in mediating impulse dyscontrol.

Alleles↗
PubMed2003

Ability of the matrix protein of vesicular stomatitis virus to suppress beta interferon gene expression is genetically correlated with the inhibition of host RNA and protein synthesis.

The vesicular stomatitis virus (VSV) matrix (M) protein plays a major role in the virus-induced inhibition of host gene expression. It has been proposed that the inhibition of host gene expression by M protein is responsible for suppressing activation of host interferon gene expression. Most wild-type (wt) strains of VSV induce little if any interferon gene expression. Interferon-inducing mutants of VSV have been isolated previously, many of which contain mutations in their M proteins. However, it was not known whether these M protein mutations were responsible for the interferon-inducing phenotype of these viruses. Alternatively, mutations in other genes besides the M gene may enhance the ability of VSV to induce interferons. These hypotheses were tested by transfecting cells with mRNA expressing wt and mutant M proteins in the absence of other viral components and determining their ability to inhibit interferon gene expression. The M protein mutations were the M51R mutation originally found in the tsO82 and T1026R1 mutant viruses, the double substitution V221F and S226R found in the TP3 mutant virus, and the triple substitution E213A, V221F, and S226R found in the TP2 mutant virus. wt M proteins suppressed expression of luciferase from the simian virus 40 promoter and from the beta interferon (IFN-beta) promoter, while M proteins of interferon-inducing viruses were unable to inhibit luciferase expression from either promoter. The M genes of the interferon-inducing mutants of VSV were incorporated into the wt background of a recombinant VSV infectious cDNA clone. The resulting recombinant viruses were tested for their ability to activate interferon gene expression and for their ability to inhibit host RNA and protein synthesis. Each of the recombinant viruses containing M protein mutations induced expression of a luciferase reporter gene driven by the IFN-beta promoter and induced production of interferon bioactivity more effectively than viruses containing wt M proteins. Furthermore, the M protein mutant viruses were defective in their ability to inhibit both host RNA synthesis and host protein synthesis. These data support the idea that wt M protein suppresses interferon gene expression through the general inhibition of host RNA and protein synthesis.

Animals↗
PubMed1997

Genetic correlates of social behaviour in wild chimpanzees: evidence from mitochondrial DNA

This study explored some aspects of chimpanzee social behaviour using mitochondrial DNA sequence data as an index of matrilineal relatedness. The hypothesis tested was that matrilineal relatedness predicts social affiliative preference in wild chimpanzees. Several behavioural measures of individual social preference were examined for chimpanzees from Kanyawara community in Uganda's Kibale Forest. None of the four pairs of strongly affiliative males in this community could have been maternal brothers, since no pair shared the same mitochondrial DNA sequence. Fourteen chimpanzee communities outside Kibale, for which no direct behavioural data were available, were also studied by using communal nesting as a rough index of affiliative preference. Again, chimpanzees that nested together did not tend to be matrilineally related. The results suggest that kin selection is weaker than previously thought as a force promoting intra-community affiliation in chimpanzees.1997The Association for the Study of Animal Behaviour

Journal Article↗
PubMed1996

The clinical and genetic correlates of MRI findings in myotonic dystrophy.

Amplification of an unstable CTG trinucleotide repeat sequence in a protein kinase gene on chromosome 19 has recently been recognised as the molecular basis of myotonic dystrophy (DM), a multi-system disorder with a wide spectrum of muscular and extramuscular manifestations. The CTG expansion of 40 patients was assessed by direct genotype analysis of the white blood cell DNA and correlated with MRI of the brain and muscles, and with functional clinical data. Cerebral pathology on MRI consisted of diffuse atrophy (68%), subcortical white matter lesions (65%), wide Virchow-Robin spaces (38%) and thickening of the skull (35%). Cerebral atrophy and extent of white matter disease correlated significantly with mental retardation, duration of disease and CTG fragment amplification. MRI of the muscular system showed fatty degeneration of different degrees in neighbouring muscles causing a mosaic pattern of the thigh in 38% and the calf in 44%. Muscular changes on MRI were strongly correlated with muscular impairment but less strongly with CTG expansion. Changes on MRI reflect the stage of development of tissue pathology in DM, modified by defect of the DM gene. Pathology on MRI is strongly correlated with functional deficits.

Adolescent↗
PubMed2002

Familial dyslexia: neurocognitive and genetic correlation in a large Finnish family.

Neuropsychological findings of individuals with dyslexia (n=24) from a large, three-generation Finnish family are presented. We have previously performed whole genome linkage scanning in this family and found that dyslexia in this kindred segregates with a single locus in the pericentromeric area of chromosome 3. Those included in the analyses were carefully evaluated for general cognitive ability, reading and spelling skills, and reading-related neurocognitive skills. The neurocognitive type of dyslexia segregating in this family consisted of deficits in phonological awareness, verbal short-term memory, and rapid naming. Severe dyslexia also seemed to be connected with a general language difficulty and was most common in the eldest generation.

Adult↗
PubMed1980

Correlative genetic variation in natural populations of cats, mice and men.

The study of the extent and basis of gene-enzyme variation has long been a principal concern of population genetics. Numerous surveys have indicated considerable amounts of genetic variation detectable in natural populations, with few exceptions. The variances of average heterozygosities (H) between species and among populations within species are large, prompting Lewontin to emphasize the importance of large gene sample sizes and Selander to encourage analysis of variation of homologous gene-enzyme systems when making species comparisons. We present here a comparative genetic analysis of electrophoretic variation at 57 homologous biochemical loci of cats, mice and men. The distribution of polymorphism among the sampled loci in the three species was nonrandom. A large group of sampled loci (60%) were monomorphic in all three species, whereas a second group (30%) of the loci were polymorphic in two or more species. This conservation of the tolerance of genetic polymorphism is apparently more a characteristic of a particular locus than of the vertebrate species or of the genome. The current hypotheses for classifying polymorphic and monomorphic loci in terms of physiological and physical enzyme characteristics have been re-examined.

Animals↗
PubMed2003

Combined pituitary hormone deficiency in Australian children: clinical and genetic correlates.

OBJECTIVE: Mutations in the gene for the POU domain transcription factor POU1F1 (human Pit-1) have been reported in patients with GH, TSH and PRL deficiencies. PROP1 (Prophet of Pit-1) gene mutations also cause gonadotrophin deficiencies and in some cases partial ACTH deficiency. This study analyses the POU1F1 and PROP1 genes in a cohort of Australian children with combined pituitary hormone deficiency (CPHD) and correlates results with patient phenotype. PATIENTS AND DESIGN: Genomic analysis was carried out on 33 patients with CPHD referred from centres around Australia. Clinical data were collected from medical records and referring physicans. RESULTS: POU1F1 mutations were identified in two of four patients with a suggestive phenotype. In a female patient, novel compound heterozygous POU1F1 mutations were identified: Arg143Leu in exon 3 and Leu194Gln in exon 4. This patient presented with failure to thrive at 6 weeks of age and has deficiencies of TSH and GH. A previously described heterozygous Arg271Trp mutation in exon 6 of the POU1F1 gene was identified in a female infant who presented with growth failure and was diagnosed with TSH then GH deficiencies. No PROP1 mutations were identified; however, we describe a number of previously unreported PROP1 polymorphisms. No patients presenting with deficiencies of all anterior pituitary hormones early in life had POU1F1 or PROP1 gene mutations. CONCLUSIONS: In 33 Australian children with CPHD we have identified POU1F1 mutations in two patients and no PROP1 mutations. We speculate that in the majority of children other genes must be responsible for the CPHD phenotype.

Adolescent↗
PubMed2004

Biochemical and molecular genetic correlation in adenylosuccinate lyase deficiency.

An homology model of human adenylosuccinate lyase structure shows that P100A substitution distorts the amino acid chain of domain I in the proximity of His-86, which behaves as general acid in the catalysis, and may expose Cys-98 and Cys-99 to oxidising agents. This model is in line with the observation that the defective protein is strongly inhibited by 4-hydroxy-2-nonenal, an hydroxyalkenal that is known to form thio-ether linkage with proteins.

Adenylosuccinate Lyase↗
PubMed1997

Identification and sizing of the GAA trinucleotide repeat expansion of Friedreich's ataxia in 56 patients. Clinical and genetic correlates.

Fifty-six patients with a clinical diagnosis of Friedreich's ataxia were investigated for the GAA trinucleotide repeat expansion recently found within the gene X25 on chromosome 9. All 56 were found to be homozygous for the expansion, with all but two patients having alleles of differing sizes. The expansion size ranged from 2 to 5 kb, with normal alleles around 1.5 kb. Sizing of the single copy of the expansion in eight sets of parents revealed marked instability in the transmission of the expansion, with both increases and decreases in allele size seen. In Friedreich's ataxia patients there was a significant inverse correlation seen between the average of the two expansions sizes and age of onset of symptoms. The GAA repeat expansion was found in the homozygous state in atypical cases of Friedreich's ataxia, such as older age of onset, preservation of lower limb reflexes and cardiac presentations. In three families the father had onset of spinocerebellar ataxia as an adult, and in two the possibility of partial expression in heterozygote carrier fathers has been raised. More importantly, the history of an ataxic syndrome in a parent does not exclude the diagnosis of Friedreich's ataxia in the offspring, and tests for the expansion should be carried out. The third family with an affected father conforms to previously described 'pseudodominant' inheritance.

Adolescent↗
PubMed1976

Dynamics of correlated genetic systems. I. Selection in the region of the Glued locus of Drosophila melanogaster.

The dynamical behavior of chromosomal segments undergoing strong selection was investigated in four replicate populations of Drosophila melanogaster. This was accomplished by following the joint behavior of allozyme markers at the loci phosphoglucomutase and esterase C, adjacent to the recessive lethal locus Glued, during and following the course of selection against Glued. The results show strong selection at other loci in the region of the marked segment. Examination of the joint dynamic of the two markers indicates that there must be more than one, and probably several, selected loci in the region under observation, with large epistatic effects. The mode of selection on the segment often results in excess heterozygosity at the markers, but does not appear to be constant in time. It is concluded that the density of selective effects in the region under study is substantial.

Alleles↗
PubMed1978

Dynamics of correlated genetic systems. IV. Multilocus effects of ethanol stress environments.

Four replicate populations of Drosophila melanogaster, two reared on medium supplemented with ethanol and two reared on standard medium, were electrophoretically monitored for 28 generations. During the first 12 generations, allelic, genotypic and gametic frequencies were determined for eight polymorphic enzymes: GOT, alpha-GPDH, MDH, ADH, TO, E6, Ec and ODH. Samples from generation 18 and 28 were electrophoretically typed for ADH and alpha-GPDH. In addition, samples from generation 27 were analyzed for the presence of inversion heterozygotes. The experimental results showed rapid gene-frequency divergence between control and treatment populations at the Adh locus in a direction consistent with the activity hierarchy of Adh genotypes. Gene-frequency divergence between control and treatment populations also occurred at the alpha-Gpdh locus, although the agreement among replicates appeared to have broken down by generation 28. No differential gene-frequency change occurred at any of the six remaining marker loci. Furthermore, values of linkage disequilibria among all linked pairs of genes were initially small and remained small throughout the course of the experiment. Taking these facts into account, it is argued that the gene-frequency response observed at ADH is most probably caused by selection at the Adh locus. The gene frequency response at alpha-Gpdh can also be be accounted for in terms of the effect of ethanol on energy metabolism, although other explanations cannot be excluded.

Alcohol Oxidoreductases↗
PubMed2000

Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive disorder with a frequency of 1 in 50 000 live births. In 97% of patients it is caused by the abnormal expansion of a GAA repeat in intron 1 of the FRDA gene on chromosome 9, which encodes a 210 amino acid protein called frataxin. Frataxin is widely expressed and has been localized to mitochondria although its function is unknown. We have investigated mitochondrial function, mitochondrial DNA levels, aconitase activity and iron content in tissues from FRDA patients. There were significant reductions in the activities of complex I, complex II/III and aconitase in FRDA heart. Respiratory chain and aconitase activities were decreased although not significantly in skeletal muscle, but were normal in FRDA cerebellum and dorsal root ganglia, although there was a mild decrease in aconitase activity in the latter. Mitochondrial DNA levels were reduced in FRDA heart and skeletal muscle, although in skeletal muscle this was paralleled by a decline in citrate synthase activity. Increased iron deposition was seen in FRDA heart, liver and spleen in a pattern consistent with a mitochondrial location. The iron accumulation, mitochondrial respiratory chain and aconitase dysfunction and mitochondrial DNA depletion in FRDA heart samples largely paralleled those in the yeast YFH1 knockout model, suggesting that frataxin may be involved in mitochondrial iron regulation or iron sulphur centre synthesis. However, the severe deficiency in aconitase activity also suggests that oxidant stress may induce a self-amplifying cycle of oxidative damage and mitochondrial dysfunction, which may contribute to cellular toxicity.

Aconitate Hydratase↗