PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Multifactorial Inheritance”

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 1,045 records · Page 58Linked to original sources
PubMed2000

Late-onset neurodegenerative diseases--the role of protein insolubility.

Recently, mutations of the alpha-synuclein gene were found to cause dominantly inherited Lewy-body Parkinson's disease (PD) and alpha-synuclein was identified as a major component of the Lewy body. However, the cause of the common form of PD, with a multifactorial rather than autosomal dominant inheritance pattern, remains unknown. Alpha-synuclein precipitates slowly and apparently spontaneously at high concentration in solution and the mutations that cause PD accelerate precipitation. Other dominantly inherited late-onset or adult-onset dominantly inherited neurodegenerative diseases are associated with precipitation of proteins. In Alzheimer disease, beta-amyloid and tau abnormalities are present and in prion disorders, prion proteins are found. In Huntington disease, a disorder with expanded CAG repeats, huntingtin precipitates occur. In dominantly inherited spinocerebellar ataxias, also expanded CAG repeat disorders, the corresponding ataxin protein precipitates are found. In multiple system atrophy, alpha-synuclein precipitates are encountered and in progressive supranuclear palsy, tau precipitates occur. In familial amyotrophic lateral sclerosis, a group of dominantly inherited disorders, SOD1 precipitates are found. Most of these disorders can involve the basal ganglia in some way. Since similar processes seem to affect neurons of adults or older individuals and since a relatively limited group of proteins seems to be involved, each producing a form of neurodegeneration, it is possible that certain common features are present that affect this group of proteins. Candidates include a conformational shift, as in prions, an abnormality of the ubiquitin-proteosome pathway, as seen in PD, an abnormality of a pathway preventing precipitation (e.g. chaperonins), or potentiation of a pathway promoting precipitation (e.g. gamma-glutamyl-transpeptidase) or apoptosis. Elucidation of the pathways causing this protein insolubilisation is the first step towards approaching prevention and reversal in these late-onset neurodegenerative diseases.

Adult↗
PubMed1996

Family study and segregation analysis of Tourette syndrome: evidence for a mixed model of inheritance.

To investigate the transmission of Tourette syndrome (TS) and associated disorders within families, complex segregation analysis was performed on family study data obtained from 53 independently ascertained children and adolescents with TS and their 154 first-degree relatives. The results suggest that the susceptibility for TS is conveyed by a major locus in combination with a multifactorial background. Other models of inheritance were definitively rejected, including strictly polygenic models, all single major locus models, and mixed models with dominant and recessive major loci. The frequency of the TS susceptibility allele was estimated to be .01. The major locus accounts for over half of the phenotypic variance for TS, whereas the multifactorial background accounts for approximately 40% of phenotypic variance. Penetrance estimates suggest that all individuals homozygous for the susceptibility allele at the major locus are affected, whereas only 2.2% of males and 0.3% of females heterozygous at the major locus are affected. Of individuals affected with TS, approximately 62% are heterozygous and approximately 38% are homozygous at the major locus. While none of the families had two parents affected with TS, 19% of families had two parents affected with the broader, phenotype, which includes TS, chronic tic disorder, or obsessive-compulsive disorder.

Adolescent↗
PubMed2005

[Multifactorial diseases: a nightmare for the geneticist].

Common diseases are often familial, but they do not show in most families, a simple pattern of inheritance. In a few families these diseases may be caused by a mutation in a single gene. In most families these diseases are multifactorial, they result from a complex interaction between a genetic component which is often polygenic and many environmental factors. Two major, model free, methods are used to locate and identify susceptibility genes that predispose to multifactorial diseases. The first is a non parametric linkage analysis that relies on affected sib pairs, or an affected pedigree member, the second method is association studies which looks for increase frequency of particular alleles or genotypes in affected compared with unaffected individuals in the population. Most of the results have not been replicated, identifying susceptibility genes is proving much more difficult than most geneticists imagined 20 years ago. The main reason for this irreproducibility is genetic heterogeneity.

Adoption↗
PubMed1998

Lack of evidence of a major gene acting on postaxial polydactyly in South America.

Data on polydactyly were obtained from two large samples: the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and from a migrant Northeastern Brazilian population of rural origin (Hospedaria). ECLAMC is a case-control clinical epidemiological program comprising 10,035 individuals distributed among 2,030 segregating nuclear families. Hospedaria data consisted of 6,586 examined individuals belonging to 1,040 nuclear families. Using complex segregation analysis methodology we found no evidence of two loci (a major gene and a modifier locus) acting on postaxial polydactyly in the present study. Very high heritability values (in a classical multifactorial model) of postaxial polydactyly were detected, for several sets of analyses in ECLAMC and in Hospedaria. For the whole ECLAMC sample there is a peculiar suggestion of a major recessive gene effect responsible for the trait; however, no comparison with a model involving transmission probabilities (tau) was possible in this highly heterogeneous sample. If the whole ECLAMC sample is divided in subsamples, according to Black admixture proportions, the same multifactorial picture emerges. Two different inheritance patterns were verified for hand (HP) and foot (FP) postaxial polydactyly: For HP there is evidence of a non-Mendelian transmission mechanism, while for FP the parental/sib transmission appears to be due only to multifactorial causes.

Brazil↗
PubMedDate not supplied

Risk of recurrence of craniospinal anomalies.

The authors analyzed 1,655 situations from their Genetic Counseling Service over a 15 year period where the reason for counseling was craniospinal anomaly (neural tube defects and/or hydrocephalus) in the family. Excluding the obviously monogenically inherited cases, they investigated pregnancies undertaken after 1,285 isolated and 177 multiple forms of craniospinal abnormalities. The recurrence rate of craniospinal defects was found to be 3.66%, which is about ten times higher than the general population risk, supporting the theory of the multifactorial threshold model in the inheritance of these anomalies. The recurrence risks of neural tube defects and of hydrocephalus were 3.47% and 2.95%, respectively. The authors concluded that recurrence risk is mainly influenced by the pathoanatomic severity of the involved anomaly, the degree of relationship, and the number of affected relatives in the family. There is a positive correlation between the pathoanatomic severity of the anomaly in the proband and the offspring. At least in one-half of the cases the same type of anomaly was observed again in the offspring as in the proband. Attention is drawn to the fact that hydrocephalus (ventriculomegaly) is often manifested only in the second half of gestation. Therefore, performing ultrasound examination is strongly recommended not only at the 18th but at the 24th week of gestation, as well in pregnancies with a positive history of neural tube defects and/or hydrocephalus.

Family Health↗
PubMed1982

[Inheritance of psoriasis. Analysis of 2035 family histories].

Detailed pedigrees were established in 2,035 families with psoriasis, including 30 twin pairs, and evaluated by means of computer analysis. The following results on the devolution of psoriasis were drawn: the hypotheses of the irregular dominant and the bifactorial recessive inheritance appear to be inacceptable. The findings suggest a multifactorial etiology of psoriasis with a polygenic mode of inheritance. The risk for relatives to be affected by psoriasis is calculated.

Adult↗
PubMed2002

[A study on the genetic epidemiology of hepatocellular carcinoma].

OBJECTIVE: To explore the interaction between inheritance and environment with the aid of research on the genetic modes of hepatocellular carcinoma (HCC). METHODS: A genetic epidemiological study of HCC was conducted based on the methods of Penrose, simple segregation and Falconer for 100 proband pedigrees from HBsAg positive cohort. The proband samples came from a cohort of 90,00 people who were followed for 8 years. Analyses on genetic modes were carried out and heritability was calculated through the comparison of the proband pedigrees incidence frequency with incidence frequencies of the cohort and general population. RESULTS: The incidence frequency of first-degree relatives was 4.0%, higher than what was seen in the general population incidence frequency (0.44%) and the cohort (1.03%). A familial aggregation of HBsAg carriers and a strong positive correlation between HBsAg carrier status and HCC were noticed (OR = 8.44, 95% CI: 3.37-20.06, P < 0.001). A ratio of the incidence frequency among siblings to the incident frequency among general population (s/q) approached 1/q(1/2) by Penrose method, but simple segregation did not show agreement with single-gene inheritance. The heritability from positive cohort was 42% +/- 6% (P < 0.05), compared with the heritability (59% +/- 7%) of general population. When the effect of the HBsAg was under control, the heritability from positive cohort turned to be 29% +/- 8% (P < 0.05), compared with the heritability (47% +/- 7%) of general population. CONCLUSION: Our findings suggested that HCC followed a multifactorial mode rather than single inheritance. An interaction effect of inheritance and environment on HCC was also noticed.

Carcinoma, Hepatocellular↗
PubMed1984

The mode of inheritance of psoriasis: evidence for a major gene as well as a multifactorial component and its implication for genetic counselling.

Complex segregation analysis of Lomholt's family data on psoriasis on the Faroe Islands gave evidence for an additive major gene with gene frequency of 0.07 and penetrance 0.12 and 0.44 in the heterozygote and in the homozygote, respectively. In addition, there was a multifactorial component with heritability 0.87. The implications of these findings for genetic counseling are discussed and analytical risk figures are presented for chosen pedigrees.

Age Factors↗
PubMed1990

The problem of polygenic disease.

Most diseases have a genetic component. In those caused by a mutation at a single locus and with a clear phenotype (Mendelian disorders) the molecular genetics approach is relatively simple. The identification and cloning of the mutated gene leads to a complete analysis of the underlying molecular pathology and usually explains variation in incidence and severity. However, most adult diseases are not of this type. Coronary heart disease, cancer, diabetes, arthritis and mental illness all have a genetic component but are rarely inherited in a Mendelian fashion. Multifactorial diseases have both genetic and environmental components which contribute in different proportions in a given patient or family. The genes involved may exert additive effects, or act synergistically. Other cases of the same disease may be entirely environmental in their causation. Molecular genetics facilitates investigation of the number of genes involved in cases of multifactorial disease, their relative weight in different families and in the community, and the nature of their interaction. One particularly powerful approach is to study a large family in which simple Mendelian segregation occurs for a disease which is more often complex or sporadic.

Coronary Disease↗
PubMed1982

The genetics of malignant hyperthermia: evidence for heterogeneity.

Study of phenotype and familial distribution of malignant hyperthermia (MH) suggests heterogeneity with MH possibly being a symptom of several disorders. Review of all reported family studies supports the concept of heterogeneity with autosomal dominant inheritance in about one-half of the families. There is no strong evidence for other mendelian patterns of inheritance, but sporadic and possibly multifactorially determined cases are common. MH is also seen in other musculoskeletal disorders. We report 12 Wisconsin families with MH and outline a preliminary approach to the counseling of MH patients and their families.

Bone Diseases↗
PubMed1984

Familial congenital diaphragmatic defects: aspects of etiology, prenatal diagnosis, and treatment.

We present 14 familial cases from five Finnish families affected with a life-threatening congenital diaphragmatic defect (CDD) and review data on 53 previously published familial cases. CDD occurred in three sibs and their half brother's son, and probably in all four offspring of parents consanguineous as both first and second cousins. In the remaining three Finnish families and in the vast majority of the previously reported familial cases, only two sibs were affected. Two thirds of those affected were males both in the Finnish and the overall series. Pedigree data, delayed fusion of the diaphragm as the primary pathogenetic mechanism, varying anatomical structure of the defective hemidiaphragm, association with other congenital anomalies, and data on animal experiments are more in accordance with multifactorial determination than with recessive inheritance. This does not exclude other genetic causes in some familial cases. The recurrence risk for sibs after one affected sib is about 2%. As the prognosis, especially in familial cases of CDD has remained grave, the development of fetal surgical treatment is desirable. This emphasizes the future role of prenatal diagnosis by ultrasound.

Consanguinity↗
PubMed1985

Familial aggregation of small congenital nevomelanocytic nevi.

We investigated the genetic aspects of congenital nevomelanocytic nevi (CNN) by comparing the prevalence rate of CNN in sibs of probands to that of CNN in newborn infants. Probands included all individuals with small (less than 40 mm) CNN registered photographically during 1982 in a children's hospital dermatology service. A CNN was defined on the basis of gross appearance and presence (according to parents) within the first 2 weeks of life. The 39 probands with small CNN had a total of 65 sibs. Eight of the 65 (12.3%) also had one or more small CNN. This prevalence rate in sibs is 11 times the population-based prevalence rate of CNN in newborn infants (1.1%) based on a published report surveying newborn infants in the same city within the past decade. In five of our 39 study families we also detected an affected parent with CNN. We conclude that small CNN may aggregate in families. Autosomal dominant inheritance with incomplete penetrance or multifactorial determination could account for this observation.

Adolescent↗
PubMed2006

Family study of the inheritance of pectus excavatum.

BACKGROUND: The most common congenital deformity of the chest wall is pectus excavatum, a malformation that is present in between 1 in 400 and 1 in 1000 live births and causes the body of the sternum to be displaced, producing a depression. There are many different shapes of the pectus, and multiple factors probably contribute to the final form. The etiology of pectus excavatum is uncertain, but a familial tendency has been found in clinical experience, where it may be seen in more than one sibling. Pectus excavatum is commonly associated with connective tissue disorders such as Marfan and Ehlers Danlos syndromes. Extensive literature review failed to identify articles documenting families with multiple affected members. PURPOSE: The purpose of this study was to collect evidence that pectus excavatum is familial and may be an inherited disorder. METHODS: Using the Children's Surgical Specialty Group database at Children's Hospital of The King's Daughters, families with more than one affected individual were selected. With Institutional Review Board-approved informed consent, 34 families agreed to participate. Family histories were obtained, and a 4-generation pedigree was constructed for each family. Forty questions were asked about each individual's medical history, and comprehensive systems review included features of connective tissue-related problems. Inheritance patterns for each family were determined by pedigree analysis. RESULTS: A total of 14 families suggested autosomal dominant inheritance, 4 families suggested autosomal recessive inheritance, and 6 families suggested X-linked recessive inheritance. Ten families had complex inheritance patterns. Pectus excavatum occurred more frequently in males than in females (1.8:1). Long arms, legs, and fingers; high-arched palate; mitral valve prolapse; heart arrhythmia; scoliosis; double jointedness; flexibility; flat feet; childhood myopia; poor healing; and easy bruising were commonly associated with pectus excavatum. CONCLUSIONS: Pedigree analysis of 34 families provides evidence that pectus excavatum is an inherited disorder, possibly of connective tissue. Although some families demonstrate apparent Mendelian inheritance, most appear to be multifactorial.

Female↗
PubMed1989

Dominantly inherited cleft lip and palate in two families.

Two families with non-syndromic cleft lip and cleft palate are described. The linear pattern of inheritance through several generations is difficult to explain by conventional multifactorial models. The pedigrees strengthen the suggestion that a dominantly inherited mutation exists with a major influence on clefting of the lip and palate alone.

Adult↗
PubMed1980

Segregation analysis of schizophrenia under a mixed genetic model.

Family data were collected on a multi-ethnic cohort of hospitalized schizophrenics in Hawaii in 1942. Results showed that prevalence rates for Orientals were significantly higher (p less than 0.001) than rates for Caucasians, Polynesians and others. Complex segregation analysis using a generalized mixed genetic model was performed on 507 sibships collected under both complete and incomplete selection. Likelihood ratio tests between the generalized model and two subhypotheses of a major gene effect and a polygenic effect revealed that neither subhypotheses could be rejected at the 5% level of significance. While neither hypothesis could be adequately supported by the likelihood ratio test, certain aspects of the findings suggest a preference for the multifactorial model in explaining the inheritance of schizophrenia in these data.

Asian People↗
PubMedDate not supplied

BRCA1 gene testing for breast and ovarian cancer in one family.

Most breast cancer is multifactorial in origin, but dominantly inherited genes are implicated in the development of approximately 5-10% of breast cancer as a whole. The identification of the BRCA1 gene, thought to account for 2% of all breast cancer and be present in almost all families affected by breast and ovarian cancer, makes testing for susceptibility to breast and ovarian cancer possible for the few families in which researchers have identified a gene mutation. Genetic counselling, by medically qualified geneticists, is available for people with rare genetic conditions caused by gene mutations. In this article, the authors describe their first experience of BRCA1 gene testing in 23 family members. They identify a unique role within a new specialty, cancer genetics, for specialist nurse practitioners in genetic testing and counselling.

Adolescent↗
PubMed1979

Genetic screening in Western Australia.

The wider application of genetic screening is described in four Western Australian populations. Counselling with prenatal diagnosis of Down's syndrome was offered to 57 women over the age of 35 years and less than 16 weeks' gestation who attended an antenatal outpatients department. Forty-four women consented to amniocentesis and two affected fetuses were found. Both public and private patients can be screened to detect fetuses with Down's syndrome. In a population of 200 pregnant girls whose infants were intended for adoption, a specially designed family history form aided identification of genetic disorders in 32 families. Counselling was offered to the biological parents, to the adoptive parents, and, prospectively, to the child in later years. The effectiveness of the family history as a screening device is illustrated in this adoption sample. Counselling of parents of 20 decreased malformed infants initiated the genetic counselling clinic in Western Australia and led to subsequent referral of 92 similar cases by the family doctors. It was found that parents who gave birth to malformed infants welcome information and risk figures. Diagnostic screening in a population of 6000 intellectually handicapped individuals yielded 1372 cases (23%) with Mendelian, multifactorial, or chromosomal modes of inheritance. This screening enabled patients with inherited causes for their intellectual handicap to be identified and placed on a register for health planning.

Abortion, Induced↗