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Results for “Multifactorial Inheritance”

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At least 19 recordsLinked to original sources
PubMed2004

Multiple rare variants in different genes account for multifactorial inherited susceptibility to colorectal adenomas.

Clear-cut inherited Mendelian traits, such as familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, account for <4% of colorectal cancers. Another 20% of all colorectal cancers are thought to occur in individuals with a significant inherited multifactorial susceptibility to colorectal cancer that is not obviously familial. Incompletely penetrant, comparatively rare missense variants in the adenomatous polyposis coli gene, which is responsible for familial adenomatous polyposis, have been described in patients with multiple colorectal adenomas. These variants represent a category of variation that has been suggested, quite generally, to account for a substantial fraction of such multifactorial inherited susceptibility. The aim of this study was to explore this rare variant hypothesis for multifactorial inheritance by using multiple colorectal adenomas as the model. Patients with multiple adenomas were screened for germ-line variants in a panel of candidate genes. Germ-line DNA was obtained from 124 patients with between 3 and 100 histologically proven synchronous or metachronous adenomatous polyps. All patients were tested for the adenomatous polyposis coli variants I1307K and E1317Q, and variants were also sought in AXIN1 (axin), CTNNB1 (beta-catenin), and the mismatch repair genes hMLH1 and hMSH2. The control group consisted of 483 random controls. Thirty of 124 (24.9%) patients carried potentially pathogenic germ-line variants as compared with 55 ( approximately 12%) of the controls. This overall difference is highly significant, suggesting that many rare variants collectively contribute to the inherited susceptibility to colorectal adenomas.

Adenoma↗
PubMed1977

Prevention of inherited multifactorial diseases.

Among the inherited multifactorial diseases are included a number of the common chronic diseases of adults. Assignment of risks within high-risk families, based on both genetic and environmental factors, offers opportunity for prevention of a portion of the present chronic disease burden. The most realistic option for prevention must be assessed for each disease, since this varies from no options to a relatively simple decision to avoid a specific environmental risk factor. Attention to specific options for prevention is an aid to identifying areas of high priority research, such as (1) factors which influence compliance with preventive management, (2) the quality of the physician-patient relationship, (3) environmental monitoring and technics for assessing genetic susceptibility to environmental risks, and (4) education of physicians in the art of chronic disease prevention.

Breast Neoplasms↗
PubMed2003

Our neglect of the normal variation is linked to a reluctance to accept multifactorial inheritance and the role of environment.

One of the most surprising evolutionary discoveries is that wild species similar to human contain a vast reservoir of variability. Why are we persistently reluctant to discuss normal variation in brain structure and function and label any deviation pathological? Despite the failure of Mendelian Genetics to solve the genetic puzzle in psychiatry, we refuse to discuss multifactorial inheritance and the role of environmental factors. Rising living conditions (high protein diet) accelerate maturation, lower pubertal age, shift body-built toward more weight for height and cerebral excitability toward higher levels. Another environmental factor which has to be provided by diet is marine fat which our brain consists of. It normalizes brain function at all levels of excitability and possibly prevents psychotic episodes if adequately supplied. As part of Human Variation in Growth and Maturation, Schizophrenia and Manic-depressive psychosis are multifactorially inherited and share susceptibility loci. They are localized at the extremes of variation. Excitability, body-built, clinical picture and CNS finding accord with this, their phenotypic characteristics might prove valuable in a hunt for genes not common to both disorders.

Brain↗
PubMed1991

The sex ratios of probands and of secondary cases in conditions of multifactorial inheritance where liability varies with sex.

Some pathological conditions affect one sex more often than the other. A curious feature of some of these conditions (dyslexia, congenital dislocation of the hip, pyloric stenosis, otosclerosis, lupus erythematosus, ankylosing spondylitis) is that the sex ratio (proportion of males) of randomly ascertained probands is more extreme than that of their affected relatives. In all these conditions, multifactorial inheritance has been suspected. A simple model is offered here of multifactorial inheritance with liability varying by sex. Under the model, such a disparity between sex ratios would be expected.

Causality↗
PubMed1978

Consanguinity in multifactorial inheritance. Application to data on congenital glaucoma.

The increase of parental consanguinity in multifactorial inheritance is evaluated by calculating the expected incidence of affected children whose parents are first cousins, using several values, namely for condition frequency and heritability of liability. This increase is compared to the expected increase in recessive inheritance, when one or more loci are involved. The method is illustrated by examples of recessive and multifactorial conditions and applied, as a test of discrimination between different modes of inheritance, to data on congenital glaucoma.

Consanguinity↗
PubMed1983

Heterogeneity between populations for multifactorial inheritance of plasma lipids.

A general linear model was described for multifactorial inheritance of the two plasma lipids, total cholesterol (CH), and triglyceride (TG). Analyses of two separate studies, the Honolulu Heart Study (HHS) and the Cincinnati Lipid Research Clinic (LRC), indicated some heterogeneity. Whereas the sibling environmental effect (b) was the only source of heterogeneity between the two studies for TG, the correlation between marital environments (u) may also be considered as a source of heterogeneity for CH. Under parsimonious hypothesis, intergenerational differences in heritabilities were not found to be significant for either trait (y1 = y2 = z1 = z2 = 1). Maternal effects were significant for CH but not for TG. Correlations between marital environments (u1 and u2) were not significant for TG, and may be considered nonsignificant for CH also under parsimonious hypotheses. In any case, the genetic (h2) and cultural (c2) heritabilities cannot be considered to be heterogeneous between the two studies. Based on pooled data, parsimonious hypothesis yields: h2 = .594 +/- .041 and c2 = .035 +/- .008 for CH, and h2 = .259 +/- .034 and c2 = .108 +/- .014 for TG.

Aged↗
PubMed1994

The maturational theory of brain development and cerebral excitability in the multifactorially inherited manic-depressive psychosis and schizophrenia.

An association has been established between the multifactorially inherited rate of physical maturation and the final step in brain development, when some 40% of synapses are eliminated. This may imply that similarly to endocrine disease entities, we have cerebral disease entities at the extremes of the maturational rate continuum. The restriction of prepubertal pruning to excitatory synapses leaving the number of inhibitory ones fairly constant, implies changes in cerebral excitability as a function of rate of maturation (age at puberty). In early maturation there will be an excess in excitatory drive due to prematurely abridged pruning, which compounds a synchronization tendency inherent in excessive synaptic density. Lowering excitatory level with antiepileptics is hypothesized to be a logical treatment in this type of brain dysfunction. In late maturation, a deficit in excitatory drive due to failure to shut down the pruning process associated with a tendency to the breakdown of circuitry and desynchronization, adds to a similar adversity inherent in reduced synaptic density. Raising the excitatory level with convulsants is hypothesized to be the treatment for this type of CNS dysfunction. The maturational theory of Kraepelin's psychoses holds that they are naturally occurring contrasting chemical signaling disorders in the brain at the extremes of the maturational rate continuum: manic depressive psychosis is a disorder of the early maturer and comprises raised cerebral excitability and a raised density of synapses. This is successfully treated with anti-epileptics like sodium valproate and carbamazepin. Schizophrenia is a disorder in late maturation with reduced cerebral excitability and reduced synaptic density. This is accordingly treated with convulsants such as typical and atypical neuroleptics. However, the conventional effective treatments in both disorders act on inhibition only by either lowering or raising inhibitory level. While the neuroleptics drugs are superior anti-psychotics they nevertheless do not affect the deviation in cerebral excitability which would explain why they do not cure. Disturbed circadian rhythms which precede psychotic episodes in manic depressives accord with a primary dysfunction in the CNS, the suprachiasmatic nucleus of the hypothalamus via its direct input the glutamatergic retinohypothalamic tract. The residual deficits in schizophrenia accord with persistently disconnected circuitry and communication which is a consequence of reduced excitatory level and is manifested in insufficient motivation, a reduced drive associated hypofunction, and neuromuscular dysfunction.

Bipolar Disorder↗
PubMed1975

[Dermatologlyphic investigations in a kindred manifesting familial atrial septal defect (ostium secundum). A contribution to the problem of genetic counselling in multifactorial inheritance (author's transl)].

In order to improve the possibilities of genetic counselling in multifactorial inheritance, dermatoglyphic investigations were performed in a family with atrial septal defect (ostium secundum) - ASD II - affecting two out of six children of a married couple and a maternal aunt. The frequency of finger-print patterns differed widely between the husband and his father on the one hand and the wife and her relatives on the other hand. Assuming some partial effect of the ASD II genes on the total gene influence on dermatoglyphics, it seemed possible that the finger-prints of the two affected siblings and of those brothers who were fairly near the threshold of ASD manifestation might resemble more closely the finger-prints of their mother and their mother's relatives than the finger-prints of their father and their paternal grandfather. This assumption was, however, disproven.

Chromosomes↗
PubMedDate not supplied

Multifactorial inheritance of white facial markings in the Arabian horse.

The hypothesis was tested that white facial markings in the Arabian horse show multifactorial inheritance. The hypothesis assumes that (1) alleles at different loci acting in a cumulative manner influence the variation in white facial markings, (2) the amount of whiteness is correlated with the number of genes, and (3) interacting nongenetic factors influence the variation. The study was based on computerized data obtained from the Arabian Horse Registry of America, Inc. The facial region was divided into five areas, and each horse was given a score according to the number of areas with a white marking. Twenty-two sire families were analyzed. Each sire family consisted of a sire, his foals, and the dams of those foals. The results of the investigation, including dam-foal and sire-foal regression analyses, were totally compatible with the hypothesis. A heritability study suggested that about two-thirds of the phenotypic variation in white facial markings among Arabian horses is attributable to genetic differences.

Animals↗
PubMed1994

Multifactorial inheritance of neural tube defects: localization of the major gene and recognition of modifiers in ct mutant mice.

Neural tube defects (NTD) in humans have been considered to have a multifactorial aetiology, however the participating genes have not been identified. The curly-tail (ct) mutant mouse develops NTD that resemble the human malformations in location, pathology and associated abnormalities. Moreover, there appears to be multifactorial influence on the incidence of NTD in offspring of curly-tail mice. We now describe a linkage analysis that localizes the ct gene to distal chromosome 4 in mice. Further analysis using recombinant inbred strains demonstrates the presence of at least three modifier loci that influence the incidence of NTD. This study provides definitive evidence for multifactorial inheritance in a mouse model of human NTD.

Abnormalities, Multiple↗
PubMed1990

Estimation of disease risk under bivariate models of multifactorial inheritance.

Adjunct consideration of both qualitative (affection status) and quantitative (correlated liability indicator) information to define a bivariate phenotype can increase considerably the accuracy and efficiency of disease risk estimation. A general approach for calculating morbid risks to offspring on the basis of parental affection status and an offspring quantitative trait is presented. We also describe two different bivariate models of multifactorial inheritance, as implemented in the computer programs POINTER and YPOINT, and make explicit their assumptions/constraints when estimating the within-person and parent-offspring correlations necessary for calculation of morbid risks. We use psychometric family data on schizophrenia from the New York High-Risk Project to estimate these correlations and illustrate our methods. Our results show that even when a trait is only moderately correlated with liability, incorporation of quantitative trait information can lead to resolution of a range of risk to offspring that is not possible through reliance on parental affection status alone. Bivariate models provide a useful methodology for incorporating quantitative indicators of liability in the investigation of genetically complex diseases.

Mathematics↗
PubMed1987

Multifactorial inheritance of abdominal aortic aneurysm.

The possible genetic predisposition to abdominal aortic aneurysm was investigated by recording the family history from 60 consecutive patients presenting for aneurysm repair. Twenty patients, age 63.2 +/- 9.3 years, had at least one first degree relative with abdominal aortic aneurysm. Thirty six patients, age 69.6 +/- 6.3 years, knew of no aortic aneurysm amongst first degree relatives and four patients could not give a full family history. A total of 25 among 320 first degree relatives (8%) or 14 amongst 192 siblings (7%) had an abdominal aortic aneurysm. Both the younger age of presentation (P less than 0.01) and the concentration of women amongst those with a positive family history argue for multifactorial inheritance of abdominal aortic aneurysm, with the genetic component calculated as approximately 70%. These same factors suggest that it might be worthwhile screening for aneurysmal disease the sibling smokers of female and younger male probands.

Aged↗
PubMedDate not supplied

The cause (multifactorial inheritance) and pathogenesis (endolymphatic malabsorption) of Meniere's disease and its symptoms (mechanical and chemical).

A clinical classification separates Meniere's disease (MD) of known cause (e.g. infection, trauma, otosclerosis, syphilis, genetic and others) from MD, idiopathic. Atypical forms of MD include vestibular MD and cochlear MD. Temporal bone studies from our laboratory and as reviewed in the literature reveal hydrops of the pars inferior, sometimes with ruptures, most often seen in Reissner's membrane, and sometimes without ruptures, to be the most important pathological correlate. Gross anatomical pathological findings include decreased mastoid and periaqueductal pneumatization and anterior displacement of the lateral sinus which reduces Trautmann's triangle. Such developmental changes most probably influence the endolymphatic absorptive system. Any explanation for the mechanisms of pathogenesis of clinical symptoms must encompass all aspects of the natural history, including vestibular symptoms, auditory symptoms, and aural pressure. Both mechanical and chemical factors best explain the clinical symptoms, and both may be traceable to multifactorial inheritance.

Ear, Inner↗
PubMedDate not supplied

Multifactorial inheritance of common white markings in the Arabian horse.

The results of a previous study were compatible with the hypothesis that common white facial markings in the Arabian horse have a multifactorial mode of inheritance. I expanded that study to (1) include the legs and therefore obtain insight into the heritability of common white markings in all peripheral regions (face and legs) of the Arabian horse and (2) investigate the influence of sex and the genotypes that produce the bay and chestnut phenotypes on the variation in common white markings. Both studies were based on computerized data obtained from the Arabian Horse Registry of America, Inc. Each leg of a horse was scored from 0 to 5 depending on the amount of whiteness present, and the four leg scores were added to obtain the total leg score for each horse. The facial region was divided into five areas, and each horse was given a score from 0 to 5 according to the number of areas with whiteness. Sire families were analyzed in which each sire family consisted of a sire, his foals, and the dams of those foals. There was a correlation between white facial scores and white leg scores, suggesting that both types of white markings are influenced by the same genetic mechanism. Sire-foal and dam-foal regression analyses were compatible with the hypothesis that common white leg markings also show multifactorial inheritance. Although the results support the model that additively acting genes (polygenes) influence the presence and extent of common white markings, the results also show that males are slightly more marked than are females and that chestnut horses are more heavily marked than are bay horses.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗