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Results for “multifactorial inheritance”

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PubMedDate not supplied

[Mode of inheritance of idiopathic generalized non-myoclonic epilepsy in families investigated by studying members with idiopathic epilepsy with tonic-clonic crises on waking. Antioquia, Colombia].

In attempt to identify the possible role of mayor genes, multifactorial inheritance, and cohort effects in the susceptibility to idiopathic epilepsy with generalized tonic clonic seizures of the awakening type (GTCS), complex segregation analysis was performed in 196 nuclear families ascertained through affected with probands with idiopathic epilepsy with GTCS belonging to the Paisa community of Antioquia (Colombia). Models postulating no transmission, single mayor locus (dominant and recessive) only, and multifactorial component only, were rejected. The models postulating no polygenic component to transmission, and no transmission of the major effect were also rejected. Thus far, complex segregation analysis suggested that a major autosomal codominant allele together with a multifactorial component (mixed model) best explains clustering of idiopathic epilepsy with GTCS in families of the Paisa community. The deficit of transmission of heterozygotes (0.17) is compatible with the existence of epistasis acting on a major gene whose frequency was estimated to be 0.0211. Its transmission variance accounts for 81% of the susceptibility to idiopathic epilepsy with GTCS. The complementary variance (19%) is due to polygenic component.

Adolescent↗

PubMed2002

Complex segregation analysis of hypospadias.

Hypospadias, when the urethra opens on the ventral side of the penis, is a common malformation seen in about 3 per 1000 male births. It is considered a complex disorder with both genetic and environmental factors involved in the pathogenesis. Low birth weight is known to be an important risk factor for hypospadias, but several observations speak in favour of genetic factors as well. In order to delineate the relative contribution of the genetic factors behind hypospadias, we performed a complex segregation analysis of 2005 pedigrees in Sweden. The probands were ascertained through the departments of paediatric surgery and departments of plastic surgery and urology in Sweden where boys with hypospadias undergo surgery. In 7% of the ascertained families one or more additional cases of hypospadias were present. The complex segregation analysis showed a heritability of 0.99 and evidence for multifactorial inheritance. The results suggest that hypospadias might be due to monogenic effects in a small proportion of the families, but that there is a multifactorial cause for the majority of the cases.

Alleles↗

PubMed1977

[Hereditary occurrence of the mesotelesystolic click syndrome: a study of 9 families (author's transl)].

Nine families affected by the mid-systolic click syndrome were studied. Of the one hundred and forty-four first-degree relatives, 117 of whom were living, eighty-four were examined. Thirty-five were found to be affected by the syndrome. Twenty-six were females and nine were males. Auscultatory and phonocardiographic findings consisted either of isolated mis-systolic clicks or systolic murmurs or a combination of the two. Electrocardiograms revealed changes of various types, most commonly of the ST-T segment. About seventy per cent of the patients were symptomatic. Nine members, not examined by the authors, had died suddenly; all had a previous history of "cardiopathy". Progressivity of mitral valve disease with age is not confirmed by the present study. It is suggested that the mode of inheritance of the defect might be that of an autosomal dominant form of Mendelian type with delayed expression of the defect. An alternatove hypothesis of a multifactorial inheritance mechanism, which is more stimulating for future studies on the cause of the syndrome, is also taken into consideration.

Adult↗

PubMedDate not supplied

Francis Galton: his approach to polygenic disease.

Gregor Mendel is considered to be the founding father of modern genetics, and his laws of inheritance have led to the successful analysis of rare monogenic diseases such as cystic fibrosis, Duchenne muscular dystrophy, familial hypercholesterolaemia, and many others. Francis Galton chose multifactorial inheritance as his starting point, and his methods of analysis have withstood the test of time. He used detailed family records to study the inherited tendency of complex traits between parents and offspring, and between identical and non-identical twins to refine the analysis, and devised new statistics to attempt to measure the extent of inheritance. For all these reasons, he can be considered the founding father of quantitative genetics.

England↗

PubMed1978

On effects of relaxed selection in familial disorders.

Theoretical predictions are made of the effect of improved treatments, with consequent increase in fertility of affected individuals, on the frequency of familial disorders. Multifactorial inheritance and some two-locus models are considered. (Changes for simple Mendelian disorders have been estimated previously by many authors.) It is estimated that, with two-locus or multifactorial models, an increase in frequency per generation of not more than a few per cent of the frequency of a disorder may be expected. The greatest increase will be in the first generation following introduction of the new treatment.

Gene Frequency↗

PubMed2003

Genetic counseling.

Medical professionals and the public are rapidly becoming aware of the overwhelming influence that an individual's genetic constitution has on fetal health and mortality, congenital malformations, cancer and other chronic diseases. Great strides have been made in recognizing and understanding modes of inheritance that had not previously been well described. Besides single-gene disorders, genetic conditions are known to be caused by a variety of different mechanisms: chromosome microdeletions and fragility, multifactorial inheritance, mitochondrial genes, triplet repeat expansions, imprinting, and uniparental disomy. Because of the complexity of genetic information, an extensive discussion is often necessary to sort out advertising, news information, and personal health concerns to enable individuals to make decisions for themselves about the various options available for testing and treatment. Genetic counseling has developed as a discipline in response to the need to educate patients, families and professionals about genetic mechanisms and their application in health care. In the future, we anticipate that the emphasis will be on primary care physicians as health-care managers, and genetic counselors will be required to educate individuals about their personal risks of inherited disorders and the implications for future generations. Genetic counseling is a process of medical education based upon empathy, patient autonomy and confidentiality in an atmosphere of empathy, support and understanding. This profession combines the knowledge of complex medical and genetic theory with the skills of a concerned, supportive counselor.

Genetic Counseling↗

PubMed2005

Genetic contributors toward increased risk for ischemic heart disease.

Cardiovascular disease is a leading cause of mortality in the United States, and is a significant cause of death worldwide. In 2002, it accounted for 38.0% of all deaths in the US, and approximately one-third of all global deaths. It has a significant economic impact, with an estimated cost in the US of 393.5 billion US dollars for 2005. The most common form of heart disease is coronary heart disease (CHD)(1)/coronary artery disease (CAD) resulting from atherosclerosis. Thirteen million Americans are affected by CHD annually, with 7.1 million of these experiencing a myocardial infarction (MI). Five to ten percent of new MI's occur in individuals younger than age 50, and the lifetime risk of developing CAD after age 40 ranges from 32% in women to 49% in men. Because of its major impact on morbidity and mortality, as well as its contribution to annual health care costs, it is of the utmost importance that improved strategies for preventing and treating CAD be developed. A promising, but inherently difficult, area of study is the identification of genes that predispose to or directly cause CAD. The identification of these genes may lead to screening tests that will allow persons at risk for developing CAD to be identified early enough that prevention/intervention strategies can be implemented to prevent or ameliorate the disease process, and may also lead to the development of gene therapy mechanisms useful in the treatment of ischemic heart disease (IHD). Because an exhaustive review of all the genes being studied in relation to CAD and MI is difficult within the confines of a review article, this review will focus on describing representative studies investigating the genes considered most likely to potentially contribute toward an increased risk for CAD and MI. Genes resulting in inherited disorders with which an increased risk of CAD and MI is associated will be discussed, as well as a number of candidate genes that may play a role in the multifactorial inheritance of CHD risk.

Coronary Artery Disease↗

PubMed1997

Identification of a complex congenital heart defect susceptibility locus by using DNA pooling and shared segment analysis.

The identification of genetic loci involved in most forms of congenital heart disease has been hampered by the complex inheritance patterns of these disorders. Atrioventricular canal defects (AVCDs) are most commonly associated with Down syndrome, although non-syndromic cases also occur. Non-syndromic AVCDs have been attributed to multifactorial inheritance. However, the occurrence of a few kindreds with multiple affected individuals has suggested that a major genetic locus can account for the disorder in some families. We have used a combination of DNA pooling and shared segment analysis to perform a high density screen of the entire autosomal human genome in an extended kindred. In so doing, we have identified a genetic locus on chromosome 1 shared by all affected individuals. Our data demonstrate the existence of a congenital heart defect susceptibility gene, inherited as an autosomal dominant with incomplete penetrance, involved in AVCD. Furthermore, our data demonstrate the power of using key isolated kindreds in combination with high density genomic screens to identify loci involved in complex disorders such as congenital heart defects.

Chromosome Mapping↗

PubMed2005

[Study on genetic epidemiology on 815 patients with vitiligo in Zhejiang area].

OBJECTIVE: Genetic factors are thought to be involved in the development of vitiligo. The aim of this study is to explore the possible genetic model of vitiligo by analyzing the genetic characteristics of 815 patients from Zhejiang province. METHODS: Data for 815 patients with vitiligo together with their first- and second-degree relatives were obtained using a standardized questionnaire. All these information was requested to confirm the answers about family history in order to reduce the possibility of 'recall' bias. The 815 probands would include 411 (50.43%) males and 404 (49.57%) females with a varied age from 2 months to 71 years old. Since the information on general prevalence of vitiligo in this area was absent, a control group was set up to facilitate the calculations of heritability degree. 468 persons of the control group were from non-vitiligo population with a sex ratio of 241(male): 227(female) with varied age of 4 months to 80 years old. Both gender and age were comparable between the vitiligo and the control population. The inheritance pattern estimation, heritability calculation and complex segregation analysis were performed with Penrose method, Falconer regression method and SAGE-REGTL program. RESULTS: In 815 vitiligo probands, 128 had and 687 had not family histories, with a heritability rate of 15.7%. The vitiligo prevalence in proband's first degree relatives was 2.580%, higher than the prevalence of 0.618% in second degree relatives, and both of them were higher than general prevalence: 0.192%. By Penrose method, the rates on different catagories were as follows: sibling prevalence rates s = 0.080 18; population prevalence rate q = 0.001 92; s/q = 41.76. The ratio of s/q did not approach 1/2q (260.42) or 1/4q (130.21), but approached 1/square root of q(22.82), suggesting vitiligo was consistent with a mode of polygenic inheritance. Using Falconer's method, heritabilities of vitiligo in first-and second degree relatives of probands were 59.61% (95% confidence interval 65.37-53.84) and 55.20% (95% confidence interval 43.88-66.52), respectively. The weighted average of heritability in all relatives was 58.7% (95% confidence interval 53.56-63.83). The results of complex segregation analysis suggested that major gene model including the Mendelian dominant, recessive and additive hypotheses were not rejected (P > 0.05). Purely environmental model and no transmission model were rejected at a 0. 001 significance level. According to AIC, Mendelian dominant inheritance was the best-fitted hypothesis. CONCLUSION: Genetic factors played an important role in the occurrence of vitiligo, and the genetic model of vitiligo could serve as the polygenetic or multifactorial inheritance with major gene trait.

Adolescent↗

PubMed1997

Age-related macular degeneration: genetics and implications for detection and treatment.

Age-related macular degeneration (ARMD) remains the most common cause of registerable blindness in the developed world. Despite extensive research, the pathogenesis of this condition remains elusive. Recent genetic advances in the understanding of inherited retinal dystrophies and the discovery of genes that code for retinal proteins have rekindled interest in the possibility of a genetic predisposition to ARMD. ARMD is most probably a disease with a multifactorial inheritance in which environmental factors can trigger disease in those who are 'genetically primed'. If it were possible to detect predisposing genes in these people, then perhaps novel therapies or preventive measures could be directed towards those at risk in the pre-symptomatic stage, in the hope of either preventing disease or decreasing its severity.

Age Factors↗

PubMed1996

[Waardenburg's syndrome].

Waardenburg syndrome is an autosomal dominant disorder characterised by sensorineural hearing loss, pigmentary abnormalities of iris, hair and skin and dystopia canthorum. The expression of clinical findings of Waardenburg syndrome is extremely variable. The potential sources of this variability include allelic variation, genetic heterogeneity, epistatic modifying genes and stochastic effects. This type of multifactorial inheritance based on oligogenic epistasis is very different from the model based on polygenic inheritance. Indeed in the first model, knowledge of the genotype at relevant modifier loci may allow prediction and possibly treatment of clinically relevant aspects of the phenotype. Therefore a more complete understanding of gene expression in Waardenburg could provide insights that are relevant to many other multifactorial diseases.

Animals↗

PubMed2002

In search for increased prevalence rates of strabismus and microstrabismus in two Bavarian districts, Oberpfalz and Niederbayern, to spot populations for gene identification.

PURPOSE: This study was intended to identify communities with an increased prevalence rate of inherited eye diseases (different forms of strabismus, juvenile maculopathy, AMD, myopia magna, etc.) in the districts Oberpfalz (Opf.) and Niederbayern (Ndb.). The data obtained in this study will serve to identify larger families and inbred populations for genetic testing to identify the cause of eye diseases with autosomal recessive and multifactorial inheritance. DESIGN: In cooperation with the local ophthalmologists in two Bavarian districts anonymized lists were compiled correlating diagnosis, postal code, and municipality of strabismus patients. The office software used in the participating practices was a limiting factor as well as the hand-written records used in most of these. The collected data were correlated with the published prevalence rates in the general population. RESULTS: Of the 104 local ophthalmologists who were invited to participate, only 17 provided information. The results indicate an increased prevalence rate of strabismus and microstrabismus patients from Neumarkt (Opf.) / Postbauer-Heng, Amberg, Hauzenberg and Pocking. CONCLUSION: Documentation as it is currently done - local ophthalmologist generally have written records and computer systems that are unsuitable for detailed surveys - restricts the possibility of completing the survey in the whole area. Nevertheless, regional accumulations of strabismus/microstrabismus could be described, providing populations for further investigations to uncover the genetic causes.

Chromosome Mapping↗

PubMed1992

Both inherited susceptibility and environmental exposure determine the low-density lipoprotein-subfraction pattern distribution in healthy Dutch families.

A lipoprotein profile characterized by a predominance of small, dense, low-density lipoprotein (LDL) particles has been associated with an increased risk of atherosclerosis. To investigate whether genetic factors are involved in determining this heavy LDL subfraction pattern, this study was undertaken with the aim of resolving the effects that major genes, multifactorial heritability, and environmental exposures have on the LDL subfraction pattern. In a random sample of 19 healthy Dutch families including 162 individuals, the distribution of the LDL subfraction pattern was determined by density gradient ultracentrifugation. For each subject a specific LDL subfraction profile was observed, characterized by the relative contribution of the three major LDL subfractions--LDL1 (d = 1.030-1.033 g/ml), LDL2 (d = 1.033-1.040 g/ml), and LDL3 (d = 1.040-1.045 g/ml)--to total LDL. A continuous variable, parameter K, was defined to characterize each individual LDL subfraction pattern. Complex segregation analysis of this quantitative trait, under a model which includes a major locus, polygenes, and both common and random environment, was applied to analyze the distribution of the LDL subfraction pattern in these families. The results indicate that the LDL subfraction pattern, described by parameter K, is controlled by a major autosomal, highly penetrant, recessive allele with a population frequency of .19 and an additional multifactorial inheritance component. The penetrance of the more dense LDL subfraction patterns, characterized by values of K < 0, was dependent on age, gender, and, in women, on oral contraceptive use and postmenopausal status. Furthermore, multiple regression analysis revealed that approximately 60% of the variation in the LDL subfraction pattern could be accounted for by alterations in age, gender, relative body weight, smoking habits, hormonal status in women, and lipid and lipoprotein levels. In conclusion, our results indicate that genetic influences as well as environmental exposure, sex, age and hormonal status in women are important in determining the distribution of the LDL subfraction patterns in this population and that these influences may contribute to the explanation of familial clustering of coronary heart disease.

Adult↗

PubMed1980

[Familial incidence in idiopathic scoliosis (author's transl)].

Fifty families with 101 of their members suffering from idiopathic scoliosis are presented. Twenty-one families were traced to 3rd degree relatives. Historical and clinical examinations were performed in all cases. In 36 patients from 18 families, HLA-A and B loci were measured, and equilibrium function was measured in 93 patients from 20 families. No significant differences were noted between the members of the 50 families studied and a previously studied control group of patients with idiopathic scoliosis with respect to age of the presentation, past history, somatic development, initial curvature and type, and response to treatment. The 21 families in whom 3rd degree relatives were traced did not show any features of a simple Mendelian inheritance. Within 39 families, however, each scoliotic member had the same type of the curve. The study of HLA-A and B loci and equilibrium dysfunction (11 cases in 93 studied, 11.8%) failed to demonstrate a familial pattern. It is concluded that the evidence presented supports the concept of a multifactorial inheritance in 50 families with 101 scoliotic members.

Adolescent↗

PubMed1984

Inheritance of idiopathic torsion dystonia among Jews.

Idiopathic torsion dystonia (ITD) has long been considered to be genetically determined, but the pattern of inheritance has been unclear. It has been suggested that inheritance may differ in Jews and non-Jews. In the present study, data gathered in a nationwide survey of ITD in Israel were analysed. Between 1969 and 1980, 47 patients were collected, of whom 40 were of European origin. In these European Jews, the ITD frequency was about 1:23 000 live births, which was five-fold greater than in Jews of Afro-Asian origin. Assuming that all cases fit the same genetic model, an X linked or a simple autosomal recessive model of inheritance did not agree well with our data. An autosomal dominant model with low penetrance could have accounted for our observations and would yield an ITD gene frequency in European Jews of 3 to 4:100 000. In view of the increased ages of their fathers, the isolated cases may have included some new mutations. Multifactorial inheritance was also possible. However, it may be inappropriate to assume that all cases have the same genetic basis, or even that all are inherited.

Dystonia Musculorum Deformans↗

PubMed1996

Complex segregation analysis of non-myoclonic idiopathic generalized epilepsy in families ascertained from probands affected with idiopathic epilepsy with tonic-clonic seizures in Antioquia, Colombia.

In an attempt to identify the possible role of major genes, multifactorial inheritance, and cohort effects in the susceptibility to idiopathic epilepsy with generalized tonic-clonic seizures of the awakening type (GTCS), complex segregation analysis was performed in 196 nuclear families ascertained through affected probands with idiopathic epilepsy with GTCS belonging to the Paisa community of Antioquia (Colombia). Models postulating no transmission, single major locus (dominant and recessive) only, and multifactorial component only, were rejected. Since the codominant single major locus model could not be rejected and models that assign no major locus to transmission, no polygenic component to transmission, and no transmission of the major effect were rejected, complex segregation analysis suggested that a major autosomal codominant allele together with a multifactorial component (mixed model) best explained clustering of idiopathic epilepsy with GTCS in families of the Paisa community. The deficit of transmission of heterozygotes (0.17) is compatible with the existence of epistasis acting on a major gene whose frequency was estimated to be 0.0211. Its transmission variance accounts for 81% of the susceptibility to idiopathic epilepsy with GTCS. The complementary variance (19%) is due to the polygenic component.

Alleles↗

PubMed1995

Inheritance of migraine investigated by complex segregation analysis.

Migraine is the most common neurological disorder, affecting about 20% of adults. The mode of inheritance was analyzed in the two main types of migraine, migraine without aura (MO) and migraine with aura (MA), by complex segregation analysis using the computer program POINTER. We included 126 probands with MO and 127 probands with MA from the general population. First-degree relatives and spouses were blindly interviewed by a neurological research fellow. The complex segregation analysis indicated that both MO and MA have multifactorial inheritance without generational difference.

Adolescent↗

PubMed1977

Genetic aspects of febrile convulsions.

A total of 6706 children 3 years of age (3491 boys, 3215 girls) in a particular geographical area in Fuchu (population approximately 182 000), Tokyo, was investigated. Some 654 children (9.8%; 10.5% for male, 9.0% for female) had had at least one convulsion, and the incidence of febrile convulsions was 6.7% (7.2% for male, 6.2% for female). The 450 FC children with febrile convulsions and 620 randomly selected control children were analyzed on the mode of inheritance. The incidence of the disease among siblings was 21.9% (29.7% after age correction), which rose greatly with increasing numbers of affected family members, and the segregation ratio among siblings was higher (36.5%) with one FC parent, and lower (18.5%) if neither parent had had a seizure. The more severe the illness in FC children, the larger the incidence among siblings. Population and family studies indicated that heredity plays an important role in febrile convulsions and that multifactorial inheritance is most likely.

Child, Preschool↗