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 1,243 records · Page 69Linked to original sources

PubMed1997

Mapping susceptibility loci in inflammatory bowel disease: why and how?

The cause of the inflammatory bowel diseases Crohn's disease and ulcerative colitis is unknown, but epidemiological evidence suggests that it is multifactorial with a strong genetic component. Several genetic loci probably contribute to disease susceptibility, accounting for the complex pattern of inheritance and heterogeneous clinical manifestations. The combination of candidate gene studies and, more recently, genome-wide searches has resulted in the identification of a number of putative susceptibility loci. With large-scale, fine-mapping studies under way, and accelerating progress in the physical mapping of the human genome, rapid progress is now being made towards the identification of the genes responsible for inflammatory bowel disease.

Animals↗

PubMed1998

Applications of DNA chips for genomic analysis.

A major frontier in medical genetics is the definition of the molecular basis of multifactorial diseases. This is especially relevant in the field of clinical psychiatry where the majority of common disorders display complex inheritance patterns, and are further influenced by environmental interactions. New technologies are needed to help address the pressing needs for discovering and deciphering the nature of such disease-associated genes. One such technology which has emerged within the past 3 years involves hybridization-based nucleic acid array (DNA chip) analysis. This technology has the potential to have a lasting impact on diverse genomic-based applications such as large-scale gene mapping studies, mutational analysis, and global expression level monitoring of all human genes. In this review we will describe the fundamental principles behind nucleic acid array-based assays, while focusing on their applications towards genome-wide DNA and RNA analysis. The current capabilities and limitations of these technologies will be discussed, with a focus on areas where future development will be needed for DNA chip-based assays to achieve their full potential.

Chromosome Mapping↗

PubMed1999

[Current ideas of hereditary nephropathies].

The paper describes a number of hereditary nephropathies, including hereditary nephritis (Alport's syndrome), the most common genetically determined renal disease, in the context of recent genetic studies. The specific features of tuberous sclerosis, a systemic disease inherited in a monogenic manner are outlined. Dysmetabolic nephropathy with oxalate-calcium crystalluria is presented as an example of multifactorial pathology.

Chromosome Aberrations↗

PubMed2000

Homozygosity for the protein S Heerlen allele is associated with type I PS deficiency in a thrombophilic pedigree with multiple risk factors.

The multifactorial character of thrombotic disease is shown in a Spanish pedigree in which the propositus, with recurrent deep vein thrombosis, inherited the factor V R/Q506 mutation, the prothrombin 20210G/A variant and type III Protein S deficiency. Among 14 relatives carrying one or two of these three risk factors, thrombosis is present in a heterozygote for R/Q506 and in another for 20210G/A, who also had slightly positive antiphospholipid antibodies. Type I PS deficiency was also found in a young asymptomatic woman. PROS1 analysis showed coexistence of type III and type I PS deficiency to be associated with heterozygosity and homozygosity, respectively, for the P460 or PS Heerlen allele of the S/P460 variant. Analysis of PS values in this and other pedigrees segregating this variant revealed that not only free but also mean total PS levels are slightly but significantly lower in the SP460 heterozygotes than in the SS460 homozygotes. These findings strongly suggest a role of the P460 variant in the expression of the PS deficient phenotype.

Adult↗

PubMedDate not supplied

[Genetics and allergy].

Complex diseases, including diseases of allergic origin (asthma, rhinitis, dermatitis), tend to cluster in families, suggesting the existence of a genetic predisposition that has been confirmed by the family and twin studies. However, it is difficult to establish a clear Mendelian pattern of inheritance and it is accepted that multiple genes exist which have an additive effect (polygeny) and interact with environmental factors (multifactorial polygenic mechanism) to cause not only the atopic constitution but also the pathology that derives from it. Advances in genetics and molecular biology, through linkage studies in chosen family nuclei and different population groups, are facilitating the location of chromosomal regions related with allergic pathology. The genes situated in these regions are considered candidate genes, and the genes themselves and the functions that they control are studied in relation to allergic disease. Although there are regions and candidate genes distributed throughout the genome, chromosomes 5, 6, 11, and 14 contain genes whose responsibility for susceptibility to atopy, asthma and bronchial hyperreactivity is accepted and whose polymorphisms could be risk factors. The study of these genes and many other candidate genes may clarify some etiopathogenic aspects of diseases of allergic origin and improve their prophylaxis and therapy.

Asthma↗

PubMed2003

Epidemiology, clinical presentation and diagnosis of onychomycosis.

Onychomycosis is a common nail disease, responsible for up to 50% of diseases of the nail. The distribution of different pathogens is not uniform; it depends on various factors such as climate, geography and migration. However, studies have revealed that two dermatophytes, Trichophyton rubrum and Trichophyton mentagrophytes, account for more than 90% of onychomycoses. Onychomycosis can be divided into four major clinical presentations: distal subungal (the most common form of the disease), proximal subungal (the most common form found in patients with human immunodeficiency virus infection), and superficial and total dystrophic onychomycosis. Onychomycosis is a multifactorial disease. Age has a very important effect on the occurrence of onychomycosis, with a correlation between increasing age and infection. Genetics has also been identified as a factor governing the epidemiology of onychomycosis; T. rubrum infection shows a familial pattern of autosomal dominant inheritance. Disease and lifestyle may also play a role in the epidemiology of fungal nail infections. Studies have shown that diabetes, acquired immunodeficiency syndrome and peripheral arterial disease may be independent predictors of onychomycosis. Because of the multifactorial nature of the epidemiology, accurate diagnosis, pertinent treatment and patient education must be paramount when treating the disease.

Adolescent↗

PubMed1983

Structured exploratory data analysis (SEDA) of finger ridge-count inheritance: I. Major gene index, midparental correlation, and offspring-between-parents function in 125 south Indian families.

Fourteen dermatoglyphic traits measured on 125 Velanadu Brahmin families were analyzed for mode of inheritance using three Structured Exploratory Data Analysis (SEDA) statistics: the major gene index, the offspring between parents function, and the traditional midparental correlation coefficient. Since the traits are integer valued with restricted ranges of variation, we simulated various transmission models with discrete expression to better understand the nature of the SEDA statistics for such variables. In addition, permutation procedures were employed to aid the interpretation of the SEDA results. These analyses suggest that corresponding homologous fingers on the left and right hands exhibit similar transmission characteristics. The relationship of the parent and child total ridge-counts of the two hands separately, as well as their combined total, virtually simulate complete Galtonian blending inheritance. Results for the individual digital ridge-counts as well as the pattern-intensity-index variable also suggest a multifactorial mode of transmission or possibly one involving several genes.

Dermatoglyphics↗

PubMed1985

Genetic factors and fetal growth sex constitution and birthweight in twins.

Fetal growth is considered a multifactorially-influenced characteristic. Genetic factors were found to play the main role in fetal growth determination, and it is the polygenic inheritance. The paper reviews the birthweights of 360 unlike-sexed two-egg twins, born at the Clinic of Gynecology and Obstetrics, Faculty of Medicine in Beograd, from January 1, 1970 through June 30, 1984. The mean birthweight differences between the male (2954.94 +/- 704.28 g) and female (2313.19 +/- 651.32 g) fetuses, amounted to 141.75 g. The difference is highly significant (P less than 0.01); variation coefficient shows that the examined groups were homogenous (VC was below 30%). The results were discussed from the genetic point of view, and particularly from the point of view of sex constitution, with special respect to the effect of Y chromosome on fetal growth. It has been known that human somatic development, body weight, bone maturation and teeth development are influenced by variety of factors. In addition to nutritional and other factors of the external environment, genetic and humoral factors are leading. The fact that fetuses with XY male constitution are heavier at birth than female fetuses with XX constitution, made us consider the correlation between genotype-phenotype, and the mentioned characteristics. This study was aimed at finding out the role of genetic factors in fetal growth, with respect to sex constitution, particularly to chromosome effect on fetal growth in unlike-sexed two-egg twins.

Birth Weight↗

PubMed2002

Genetics of osteoporosis: role of steroid hormone receptor gene polymorphisms.

Osteoporosis is a common skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. In the past years, twin and family study have shown that this disease recognizes a strong genetic component and that genetic factors play an important role in regulating bone mineral density (BMD). While in few isolate conditions osteoporosis can be inherited in a simple Mendelian pattern, due to single gene mutations, in the majority of cases has to be considered a multifactorial polygenic disease in which genetic determinants are modulated by hormonal, environmental and nutritional factors. Given the important role that steroid hormones play in bone cell development and in the maintenance of normal bone architecture, polymorphisms at receptor of the steroid/thyroid hormone receptor superfamily, such as estrogen receptor alpha (ERalpha) and Vitamin D receptor (VDR) have been thoroughly investigated in the last years and appeared to represent important candidate genes. The individual contribution of these genetic polymorphisms to the pathogenesis of osteoporosis remains to be universally confirmed and an important aim in future work will be to define their functional molecular consequences and how these polymorphisms interact with each other and with the environment to cause the osteoporotic phenotype. A further promising application of genetic studies in osteoporosis comes from their pharmacogenomic implications, with the possibility to give a better guidance for therapeutic agents commonly used to treat this invalidating disorder or to identify target molecules for new therapeutic agents.

Bone and Bones↗

PubMedDate not supplied

Epidemiology of prostate cancer.

Malignant transformation of the prostate and progression of carcinoma appear to be the consequence of a complex series of initiation and promotional events under genetic and environmental influences. Increased incidence of the condition may be the result of improved detection, greater awareness of the condition, and possibly an increased life expectancy accompanied by a decrease in competing causes of death rather than a true increase in the prevalence of the disease. The marked racial and geographic differences are probably multifactorial, with genetic, environmental, and possibly social influences affecting progression of the disease. Among several risk factors, evidence for the familial inheritance of some prostate cancers is compelling. Dietary influences, hormonal milieu, and the role of environmental carcinogens are currently under intense investigation. As further risk factors are identified, it will become increasingly important to identify individuals at increased risk for the disease. These men should undergo regular evaluation with state-of-the-art methods.

Humans↗

PubMed1988

Estimating genetic parameters of survival distributions: a multifactorial model.

For a number of genetically influenced illnesses, age of onset is correlated between relatives. In some cases, age of onset also serves as an index of an individual's inherited liability to an illness. Typically, survival models for age of onset distributions do not allow for these effects. We have used the gamma distribution as the basis of a model which specifies genetic variability in age of onset. Specifically, we allow the hazard frequency parameter of the gamma distribution to be a monotonic function of an individual's inherited liability to an illness. Simulations under various gamma models indicate that age of onset correlations may be strikingly different from correlations in liability. Maximum likelihood estimation procedures were used to obtain parameter estimates from simulated data sets and to determine whether it is possible to discriminate between gamma processes of different order. The results of 1,000 pairs of twins (500 monozygotic and 500 dizygotic) gave parameter estimates that were fairly accurate but that decreased in precision as the order of the gamma process increased. We discuss the effect this may have on inferences made about age of onset.

Age Factors↗

PubMed1995

Epidemiology and genetics of microtia-anotia: a registry based study on over one million births.

The epidemiology and genetics of microtia-anotia (M-A) were studied using data collected from the Italian Multicentre Birth Defects Registry (IPIMC) from 1983 to 1992. Among 1,173, 794 births, we identified 172 with M-A, a rate of 1.46/10,000; 38 infants (22.1%) had anotia. Of the 172 infants, 114 (66.2%) had an isolated defect, 48 (27.9%) were multiformed infants (MMI) with M-A, and 10 (5.8%) had a well defined syndrome. The frequency of bilateral defects among non-syndromic cases was 12% compared to 50% of syndromic cases (p = 0.007). Among the MMI only holoprosencephaly was preferentially associated with M-A (four cases observed upsilon 0.7 expected, p = 0.005). No significant variations were identified in the prevalence of non-syndromic cases by geographical area (range 0.62-2.37/10,000 births) or by five month time periods (range 0.21-2.58/10,000 births), nor was there evidence of time trends. When M-A cases were compared to controls, we found that mothers with parity 1 had a higher risk of giving birth to an MMI with M-A, and that mothers with chronic maternal insulin dependent diabetes were at significantly higher risk for having a child with M-A. MMI with M-A had higher rates of prematurity, low birth weight, reduced intrauterine growth, and neonatal mortality than infants with isolated M-A and controls. Babies with isolated M-A had, on average, a lower birth weight than controls; the difference was higher for females. The analysis of pedigrees and familial cases suggests an autosomal dominant trait with variable expression and incomplete penetrance in a proportion of cases, or a multifactorial aetiology. Three cases had consanguineous parents, but the absence of M-A among previous sibs does not support autosomal recessive inheritance.

Abnormalities, Multiple↗

PubMed1999

Inherited predisposition to myasthenia gravis in Newfoundlands.

Acquired myasthenia gravis was diagnosed in 6 Newfoundlands from 2 distinct lineages. Three dogs, including 1 pair of littermates, from each lineage were affected. History and clinical signs did not differ from that reported for other dogs with acquired myasthenia gravis. Although a genetic predisposition for development of certain autoimmune diseases in several species has been identified, the immunopathogenesis of myasthenia gravis is multifactorial and includes hormonal, environmental, and infectious disease factors. The high incidence of myasthenia gravis in these 2 distinct lineages of Newfoundlands, a breed with a low relative risk for development of this disease, suggests an underlying genetic mechanism. However, mode of inheritance could not be determined from this small number of dogs. Regardless, breeders should be alerted to this disorder, and they should consider removing Newfoundlands with acquired myasthenia gravis from breeding programs.

Animals↗

PubMed1986

Inherited disorders in the black population of southern Africa. Part I. Historical and demographic background; genetic haematological conditions.

Genetic, geographic and socio-economic diversity has resulted in disparity in the relative prevalence of many inherited disorders and congenital conditions in the populations of southern Africa. In the first section of a 3-part article an account is given of the historical and demographic background in relation to factors which influence the presence and frequency of faulty genes in the black community. In addition, inherited haematological conditions--in particular haemoglobinopathies, red-cell enzyme and membrane defects--are discussed in terms of their clinical, genetic and anthropological significance. The conditions transmitted by simple genetic mechanisms are documented in Part II, with discussion of those notable for their unusually high or low prevalence. In the final section multifactorial, chromosomal and non-genetic congenital disorders are reviewed and a number of unusual conditions of obscure aetiology are mentioned. In this 3-part overview an attempt has been made to document present knowledge and to provide a bibliography for inherited and congenital disorders in the black population.

Anemia, Sickle Cell↗

PubMed1993

A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10.

Hirschsprung disease (HSCR) is characterized by a congenital absence of enteric ganglia along a variable length of the intestine. Although long considered to be a multifactorial disease, we have identified linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby providing monogenic inheritance in some families. A maximum two-point lod score of 3.37 (theta = 0.045) was observed between HSCR and D10S176, under an incompletely penetrant dominant model. Multipoint, affecteds-only and non-parametric analyses supported this finding and localize this gene to a region of approximately 7 centiMorgans, in close proximity to the locus for multiple endocrine neoplasia type 2 (MEN2). The co-occurrence of these two entities in some families might be attributable to shared pathogenetic origins.

Alleles↗

PubMed2005

Haemophilia A: from mutation analysis to new therapies.

Haemophilia is caused by hundreds of different mutations and manifests itself in clinical conditions of varying severity. Despite being inherited in monogenic form, the clinical features of haemophilia can be influenced by other genetic factors, thereby confounding the boundary between monogenic and multifactorial disease. Unlike sufferers of other genetic diseases, haemophiliacs can be treated successfully by intravenous substitution of coagulation factors. Haemophilia is also the most attractive model for developing gene-therapy protocols, as the normal life expectancy of haemophiliacs allows the side effects of gene therapy, as well as its efficiency, to be monitored over long periods.

DNA Mutational Analysis↗

PubMed2003

Familial abdominal aortic aneurysms: collection of 233 multiplex families.

OBJECTIVE: This study investigated a large number of families in which at least two individuals were diagnosed with abdominal aortic aneurysms to identify the relationship of the affected relatives to the proband. SUBJECTS AND METHODS: Families for the study were recruited through various vascular surgery centers in the United States, Finland, Belgium, Canada, the Netherlands, Sweden, and the United Kingdom and through our patient recruitment website (www.genetics.wayne.edu/ags). RESULTS: We identified 233 families with at least two individuals diagnosed with abdominal aortic aneurysms. The families originated from nine different nationalities, but all were white. There were 653 aneurysm patients in these families, with an average of 2.8 cases per family. Most of the families were small, with only two affected individuals. There were, however, six families with six, three with seven, and one with eight affected individuals. Most of the probands (82%) and the affected relatives (77%) were male, and the most common relationship to the proband was brother. Most of the families (72%) appeared to show autosomal recessive inheritance pattern, whereas in 58 families (25%), abdominal aortic aneurysms were inherited in autosomal dominant manner, and in eight families, the familial aggregation could be explained by autosomal dominant inheritance with incomplete penetrance. In the 66 families where abdominal aortic aneurysms were inherited in a dominant manner, 141 transmissions of the disease from one generation to another were identified, and the male-to-male, male-to-female, female-to-male, and female-to-female transmissions occurred in 46%, 11%, 32%, and 11%, respectively. CONCLUSION: Our study supports previous studies about familial aggregation of abdominal aortic aneurysms and suggests that first-degree family members, male relatives, in particular, are at increased risk. No single inheritance mode could explain the occurrence of abdominal aortic aneurysms in the 233 families studied here, suggesting that abdominal aortic aneursyms are a multifactorial disorder with multiple genetic and environmental risk factors.

Aortic Aneurysm, Abdominal↗

PubMed2000

A common promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and fat mass in obese girls.

Mutations in the leptin gene lead to rare obese syndromes of Mendelian inheritance in humans and rodents. However, no relevant mutations are found in the coding region of leptin gene DNA in patients with common multifactorial obesity. These obese patients tend to have an elevation of serum leptin proportional to their adiposity but with a rather wide dispersion of leptin levels for a given body fat content, which in part is attributable to sexual dimorphism. The current study, performed in two independent Caucasian cohorts of obese girls, shows that a frequent promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and body fatness. Girls of comparable adiposity have different circulating leptin levels, depending on their genotype at this locus. Girls with the -/- Lep -2,549 genotype have 25% lower mean leptin levels than the girls with other genotypes, as reflected by differences in the regression slopes of leptin-to-fat mass. Therefore, genetic factors related to the leptin gene may be important in defining the set point of obese individuals (i.e., the circulating leptin level for a given degree of body fatness). This definition may be of both physiological and therapeutic relevance, although a phenotypic association with an individual single-nucleotide polymorphism is not sufficient to assign function to this particular nucleotide site.

Adipose Tissue↗