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 361 records · Page 20Linked to original sources

PubMed2002

Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients.

McKusick-Kaufman syndrome comprises hydrometrocolpos, polydactyly, and congenital heart defects and overlaps with Bardet-Biedl syndrome, comprising retinitis pigmentosa, polydactyly, obesity, mental retardation, and renal and genital anomalies. Bardet-Biedl syndrome is genetically heterogeneous with three cloned genes ( BBS2, BBS4, and MKKS) and at least three other known loci ( BBS1, BBS3, and BBS5). Both McKusick-Kaufman syndrome and Bardet-Biedl syndrome are inherited in an autosomal recessive pattern, and both syndromes are caused by mutations in the MKKS gene. However, mutations in MKKS are found in only 4%-11% of unselected Bardet-Biedl syndrome patients. We hypothesized that an analysis of patients with atypical Bardet-Biedl syndrome and McKusick-Kaufman syndrome (Group I; 15 probands) and patients with Bardet-Biedl syndrome who had linkage results inconsistent with linkage to the other loci (Group II; 12 probands) could increase the MKKS mutation yield. Both mutant alleles were identified in only two families in Group II. Single (heterozygous) sequence variations were found in three Group I families and in two Group II families. Combining these results with previously published data showed that only one mutant allele was detected in nearly half of all patients screened to date, suggesting that unusual mutational mechanisms or patterns of inheritance may be involved. However, sequencing of the BBS2 gene in these patients did not provide any evidence of digenic or "triallelic" inheritance. The frequency of detected mutations in MKKS in Group II patients was 24%, i.e., six times higher than the published rate for unselected BBS patients, suggesting that small-scale linkage analyses may be useful in suitable families.

Abnormalities, Multiple↗

PubMed2006

[Methodology of QTL's linkage analysis for discrete traits controlled by polygenes].

Many characters of biological interest and economical importance that are not inherited in a simple Mendelian fashion vary in a discrete form. These traits are called complex discrete traits. A complex discrete trait is presumably controlled by several genes, and characteristic of the trait is modified by environmental effects. Although methods of mapping QTL for continuous quantitative characters have been well developed, such methods for discrete characters are not available yet. So many non-linear methods were developed under the framework of the generalized linear model. In this paper, we reviewed the recent progress and improvement of the methods for QTL mapping in this field.

Animals↗

PubMed2004

Inherited arrhythmogenic diseases: the complexity beyond monogenic disorders.

Twelve years after the identification of the molecular bases of the long-QT syndrome, it is now possible to express some considerations on the impact that genetic findings have had in the understanding of inherited arrhythmogenic diseases. Along with the excitement for the emerging data on genotype/phenotype correlation and for the development of the first recommendations for gene-specific management of patients, it is also important to acknowledge the unexpected complexity that has emerged. The focus of this article is to analyze the elusive aspects of the relationship between genetic defects and clinical manifestations and to propose some research directions that may provide the needed answers to move forward in the understanding of the genetics of heart rhythm abnormalities.

Ankyrins↗

PubMed2001

Chromosome imbalances associated with epilepsy.

Epilepsy is among the most frequent findings in many, especially autosomal, chromosome aberrations. Its incidence, however, is very variable, and there are very few aberrations in which epilepsy is a constant finding. Even siblings and monozygotic twins with the same aberration are often discordant for seizure disorders. Similar observations can be made for congenital (major) malformations in chromosome aberrations. The common explanation is that in these instances epilepsy is not caused by the action of a single gene in single or triple dose, but is influenced by the combined action of a number of genes within and outside of the aneuploid segment. The situation is comparable to a polygenic model of inheritance. Gene mutations associated with epilepsy are known, to date, only for two disorders: the lissencephaly 1 gene in Miller-Dieker syndrome and mutations in the UBE3A gene in Angelman syndrome. Chromosome aberrations in which epilepsy is a major and consistent finding include Angelman syndrome due to loss of the maternal 15q11.2-q12 segment, tetrasomy of the maternal segment 15pter-q13 due to an additional inv dup chromosome, Miller-Dieker syndrome due to deletion of the 17p13.3 segment including the lissencephaly1 gene, ring chromosome 20, and Wolf-Hirschhorn syndrome due to deletion of at least the 4p16.3 segment.

Chromosome Aberrations↗

PubMed2001

Cross-resistance and inheritance of resistance to Bacillus thuringiensis toxin Cry1Ac in diamondback moth (Plutella xylostella L) from lowland Malaysia.

A field population of Plutella xylostella from Malaysia (SERD4) was divided into five sub-populations and four were selected (G2-G5) with the Bacillus thuringiensis insecticidal crystal (Cry) toxins Cry1Ac, Cry1Ab, Cry1Ca and Cry1Da. Bioassay at G6 gave resistance ratios of 88, 5, 2 and 3 for Cry1Ac, Cry1Ab, Cry1Ca and Cry1Da respectively compared with the unselected sub-population (UNSEL-SERD4). The Cry1Ac-selected population showed little cross-resistance to Cry1Ab, Cry1Ca and Cry1Da, (3-, 2- and 3-fold compared with UNSEL-SERD4), whereas the Cry1Ab-SEL sub-population showed marked cross-resistance to Cry1Ac (40-fold), much greater than Cry1Ab itself. In contrast, the Cry1Ca- and Cry1Da-SEL sub-population showed little if any cross-resistance to Cry1Ac and Cry1Ab. The mode of inheritance of resistance to Cry1Ac was examined in Cry1Ac-selected SERD4 by standard reciprocal crosses and back-crosses using a laboratory insecticide-susceptible population (ROTH). Logit regression analysis of F1 reciprocal crosses indicated that resistance to Cry1Ac was inherited as an incompletely dominant trait. At the highest dose of Cry1Ac tested, resistance was recessive, while at the lowest dose it was almost completely dominant. The F2 progeny from a back-cross of F1 progeny with ROTH were tested with a concentration of Cry1Ac that would kill 100% of ROTH. The mortality ranged between 50 and 95% in seven families of back-cross progeny, which indicated that more than one allele on separate loci were responsible for resistance to Cry1Ac.

Animals↗

PubMed2001

Deltamethrin resistance in the codling moth (Lepidoptera: Tortricidae): inheritance and number of genes involved.

The inheritance of deltamethrin resistance in Cydia pomonella (L.) has been investigated by crossing a resistant (Rv) and a susceptible (Sv) strain, derived from a population collected in south-eastern France in 1995. Deltamethrin resistance was suspected to be under the control of a kdr-type allele and an enhanced mixed-function oxidase (mfo). F(1) and F(2) progenies were therefore tested through dose-response and enzyme assays. Dose-response relationships indicated that resistance was inherited as an autosomal incompletely recessive (D=-0.199) character, involving at least two genes. Enzyme measures suggested the contribution of 1.2 genes to the expression of mfo, with incomplete dominance (D=0.460). Our results support the hypothesis of a polygenic response to deltamethrin selection in the Rv strain, including a major kdr-type allele with a minor effect of mfos. In the light of these findings, we consider the resistance in codling moth populations in south-eastern France as a product of an adaptive sequential selection process, occurring through the sequential addition of resistance genes.

Animals↗

PubMed2003

Complex segregation analysis of 1,792 cleft lip and palate families in South America: 1967-1997.

Although several studies have demonstrated familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL/P), its model of inheritance remains uncertain. We report the results of complex segregation analysis performed in South American families with a newborn affected with CL/P. Families of 1,792 consecutive newborns affected with CL/P and registered during the period 1967 to 1997 were studied. A model that did not include a major locus was the best-fitting model for CL/P families. This result is in agreement with previous studies which showed a significant association of several putative susceptibility loci and CL/P, indicating that the genes involved in CL/P are likely to have only a very modest impact on disease risk.

Cleft Lip↗

PubMedDate not supplied

Evidence on major gene control of cortical index in pedigree data from Middle Dalmatia, Croatia.

It was recently reported that the inheritance of the metacarpal cortical index (CI) in the Chuvashian population can be described in terms of a major gene (MG) model. By applying transmission probability tests, the hypothesis was accepted that not only baseline level of CI but also its sex-specific dependence on age were under control of the same putative large-effect gene. Using a pedigree sample from the population of the islands of Middle Dalmatia, Croatia (847 observed individuals in 278 pedigrees), data are presented to support the above findings. The following hypotheses were accepted: (i) inheritance of baseline CI in the Croatian population can be attributed to the effect of a MG responsible for about 42% of the variation; (ii) the same MG takes part in the control of the dependence of CI on age, particularly the age at onset of involutive bone changes (inflection point), and of the rate of decrease in CI with age (slope coefficient). Issues related to the assortative mating effect on CI and the determination of the most parsimonious model are discussed.

Adolescent↗

PubMed2000

A simple estimate of the general population frequency of the MHC susceptibility gene for autoimmune polygenic disease.

We wished to determine the frequencies of the MHC and non-MHC susceptibility genes for polygenic autoimmune diseases like type 1 diabetes (IDDM). We used Mendelian inheritance and the Hardy-Weinberg equilibrium to calculate the frequencies of mating pairs and susceptible offspring under classical recessive and dominant inheritance of the MHC susceptibility gene. We then analyzed the distribution of haplotype sharing by affected sib pairs of the 4 MHC haplotypes in each of the kinds of mating pairs in terms of the frequency of the disease susceptibility gene. For IDDM, the analysis was consistent with a recessive, but not a dominant, MHC susceptibility gene of frequency 0.525 at a distribution of 55, 38 and 7% of affected sib pairs who share 2, 1 and 0 MHC haplotypes, respectively. A simple relationship was obtained: if inheritance is recessive, the MHC susceptibility gene frequency is the square root of the fraction of affected sib pairs who share no MHC haplotypes multiplied by 4. For recessive inheritance, affected sib pairs who share no haplotypes are solely in families where both parents are homozygous MHC-susceptible. Although homozygous MHC susceptibles represent over 25% of the population, only 2-3% of them are IDDM-susceptible at non-MHC susceptibility loci, also required for disease expression. Predictions from our analysis fit all published observations of the familial occurrence of disease. The analysis is general, simple and provides a single estimate (not a range) of the MHC susceptibility gene frequency. This approach should be applicable to other MHC-determined polygenic diseases.

Autoimmune Diseases↗

PubMed2000

Incomplete penetrance of MHC susceptibility genes: prospective analysis of polygenic MHC-determined traits.

We propose an approach to understanding incomplete penetrance of disease susceptibility genes as a method of studying the underlying mechanisms of polygenic diseases. Incomplete penetrance is the failure of genetically susceptible individuals to exhibit a trait. We define as baseline penetrance that which occurs in genetically identical (monozygotic) twins of an index subject with a major histocompatibility complex (MHC)-associated disease or trait. We consider two mechanisms for incomplete baseline penetrance: an extrinsic (environmental) trigger and an intrinsic stochastic, gene-associated process. The latter can be detected for dominant expression because susceptibility genes in homozygotes (with their two intrinsic triggers) will be up to twice as frequently penetrant as those in heterozygotes. The extent of MHC and non-MHC gene contribution determines differences between baseline penetrance and apparent penetrance in MHC-identical sib pairs, sib pairs in general and MHC-identical unrelated individuals. Inheritance patterns in families do not reveal modes of inheritance of incompletely penetrant polygenic MHC-determined traits. A method is proposed to study such traits prospectively in persons presumed to be homozygous, heterozygous or non-carrying for susceptibility genes by determining trait expression in homozygotes, heterozygotes or non-carriers of trait-associated conserved extended MHC haplotypes. The method provides direct estimates of apparent penetrance rates, modes of genetic determination, and, if the trait is dominant, the origin of penetrance. When applied to dominant MHC susceptibility gene-determined immunoglobulin deficiencies in two populations, the ratios of affected haplotype homozygotes to heterozygotes near 2.0 were consistent with an intrinsic mechanism for baseline penetrance acting on the MHC susceptibility genes.

Environment↗

PubMed2002

[Major-polygene effect analysis of super quality fiber properties in upland cotton (G. hirsutum L.)].

The modern textile industry depends on the improvement of fiber quality, especially strength to meet the needs of higher spinning speed. Inheritance of super quality fiber properties in Upland cotton was conducted in the present paper. P1, P2, F1, B1, B2 and F2 of eight crosses from five parents with different fiber strength, i.e. 7235 x TM1, TM1 x 7235, HS42 x TM1, PD69 x TM1, MD51 x TM1, 7235 x HS42, 7235 x PD69 and HS42 x PD69, and F2:3 for 7235 x TM1, were used in the study. The materials were planted in Nanjing or Hainan in 1998 and 1999, the individual plant fiber samples were tested with HVI system in Cotton Research Institute of CAAS at Anyang. The segregation analysis methods for major genes plus polygene mixed inheritance model developed by Gai were used to identify the genetic system of fiber qualities. The results from joint analyses of multiple segregating generations as well as single segregating generations, especially for F2:3, showed one major gene plus polygene mixed inheritance model in all fiber quality characters. The heritability values of major gene in F2 of 7235 x TM1 with great parent difference were estimated as 19.6% for fiber strength, 32.0% for micronaire and 13.9% for fiber length, but little in B1 and B2 for fiber qualities. The fiber length showed high and positive dominant effect, but negative value or zero of major or polygene dominant effects for other fiber qualities. Therefore, Mid-parent value or tendency to lower parent in F1 for most of fiber qualities lead to low selection efficiency, which suggests that molecular assisted selection should be considered at first in the improvement of fiber qualities.

Cotton Fiber↗

PubMed2004

Global mapping of the yeast genetic interaction network.

A genetic interaction network containing approximately 1000 genes and approximately 4000 interactions was mapped by crossing mutations in 132 different query genes into a set of approximately 4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.

Amino Acid Sequence↗

PubMed2004

Intralocus sexual conflict can drive the evolution of genomic imprinting.

Genomic imprinting is a phenomenon whereby the expression of an allele differs depending upon its parent of origin. There is an increasing number of examples of this form of epigenetic inheritance across a wide range of taxa, and imprinting errors have also been implicated in several human diseases. Various hypotheses have been put forward to explain the evolution of genomic imprinting, but there is not yet a widely accepted general hypothesis for the variety of imprinting patterns observed. Here a new evolutionary hypothesis, based on intralocus sexual conflict, is proposed. This hypothesis provides a potential explanation for much of the currently available empirical data, and it also makes new predictions about patterns of genomic imprinting that are expected to evolve but that have not, as of yet, been looked for in nature. This theory also provides a potential mechanism for the resolution of intralocus sexual conflict in sexually selected traits and a novel pathway for the evolution of sexual dimorphism.

Animals↗

PubMed2004

Evolutionary model with genetics, aging, and knowledge.

We represent a process of learning by using bit strings, where 1 bits represent the knowledge acquired by individuals. Two ways of learning are considered: individual learning by trial and error, and social learning by copying knowledge from other individuals or from parents in the case of species with parental care. The age-structured bit string allows us to study how knowledge is accumulated during life and its influence over the genetic pool of a population after many generations. We use the Penna model to represent the genetic inheritance of each individual. In order to study how the accumulated knowledge influences the survival process, we include it to help individuals to avoid the various death situations. Modifications in the Verhulst factor do not show any special feature due to its random nature. However, by adding years to life as a function of the accumulated knowledge, we observe an improvement of the survival rates while the genetic fitness of the population becomes worse. In this latter case, knowledge becomes more important in the last years of life where individuals are threatened by diseases. Effects of offspring overprotection and differences between individual and social learning can also be observed. Sexual selection as a function of knowledge shows some effects when fidelity is imposed.

Aging↗

PubMed2002

Multiplex relative risk and estimation of the number of loci underlying an inherited disease.

Knowledge of the number of causative loci is necessary to estimate the power of mapping studies of complex diseases. In the present article, we reexamine a theory developed by Risch and its implications for estimating the number L of causative loci affecting a complex inherited disease. We first show that methods based on Risch's analysis can produce estimates of L that are inconsistent with the observed population prevalence of the disease. We demonstrate this point by showing that the maximum-likelihood estimate for L produced by the method of Farrall and Holder for cleft lip/cleft palate data is not consistent with the prevalence under the multiplicative model. We show how to incorporate disease prevalence and develop a maximum-likelihood method for estimating L that uses the entire distribution of numbers of affected individuals in families containing an affected individual. This method avoids the potential inconsistencies of the Risch method and has greater precision. We apply our method to data on cleft lip/cleft palate and schizophrenia.

Bias↗

PubMed2005

Polygenic inherited predisposition to breast cancer.

The known breast cancer predisposing genes account for only about 20% of inherited susceptibility. Epidemiological analyses suggest that much of the remaining 80% is explained by the combined effect of many individually weak genetic variants, rather than by further rare, highly penetrant mutations. In the near term, identification of variants may indicate new pathways or mechanisms in breast cancer development. The polygenic model implies a wide distribution of risk in the population. In the longer term, it may be possible to construct individual risk profiles to guide public health interventions. The search for genetic variants has so far proved difficult. A key unanswered question is the "genetic architecture" of predisposition-that is, strong or weak alleles, common or rare. We describe a genome-wide scan designed to provide a first-pass answer to this question.

Alleles↗

PubMed2005

Genetic control of the immune response in pathogenesis.

BACKGROUND: Epidemiological studies have suggested that there is a genetic component to susceptibility to chronic periodontitis. Studies in humans and in animal models have suggested that some of the important components may be polymorphisms in key immunological genes. METHODS: This paper summarizes previously published data from a mouse model in which alveolar bone loss is induced by oral infection with Porphyromonas gingivalis. Mice of different inbred immune-normal strains were used, as well as the F1 heterozygotes from crosses between strains. In addition, tissue expression of an array of immunological genes was measured in the gingiva and spleen of these mice by quantitative reverse transcription-polymerase chain reaction (QPCR). RESULTS: Not all strains of mice are susceptible to bone loss. Intercross experiments demonstrate that susceptibility is an inherited trait. A subset of immunological genes tested showed differential basal expression in the gingiva or spleens (or both). Tumor necrosis factor and osteoprotegerin mRNAs are more highly expressed in the gingiva and interleukin-1 mRNA is more highly expressed in both the gingiva and the spleens of susceptible mice than resistant mice. In the resistant mice, interleukin-15 mRNA in the gingiva and Selp mRNA in the spleen are present at higher levels. In the resistant mice no genes changed expression after P. gingivalis infection, while mRNA for interleukin-1, osteoprotegerin, and STAT6 all increased in the susceptible mice. CONCLUSIONS: Susceptibility and resistance are heritable traits. Strain differences in basal mRNA expression correlate with differences in susceptibility. Genes that change expression in response to infection also correlate with differences in susceptibility.

Alveolar Bone Loss↗

PubMed1999

Multicentre evaluation of combined prothrombotic defects associated with thrombophilia in childhood. Childhood Thrombophilia Study Group.

UNLABELLED: To evaluate the role of multiple established and potential causes of childhood thrombophilia, 285 children with a history of thrombosis aged neonate to 18 years (first thrombotic onset) were investigated and compared with 185 healthy peers. APC-resistance (FV:Q506), protein C, protein S, antithrombin, heparin cofactor II (HCII), histidine-rich glycoprotein (HRGP), and prothrombin (F.II), factor XII (F.XII), plasminogen, homocysteine and lipoprotein (a) (Lp(a)) were investigated. In 59% of patients investigated one thrombotic defect was diagnosed, 19.6% showed two thrombotic risk factors, while in 21.4% of children investigated no risk factor could be identified. Single defects comprised established causes of inherited thrombophilia: FV:Q506 (homozygous n = 10, heterozygous n = 69), protein C (homozygous n = 1; heterozygous n = 31), heterozygous type I deficiency states of protein S (n = 7), antithrombin (n = 7) and homocystinuria (n = 6); potentially inherited clotting abnormalities which may be associated with thrombophilia: F.XII (n = 3), plasminogen (n = 2), HCII (n = 1), increased HRGP (n = 4); new candidate risk factors for thrombophilia: elevated plasma levels of Lp(a) (n = 26), F.II (n = 1). Heterozygous FV:Q506 was found in combination with heterozygous type I deficiency states of protein C (n = 2), protein S (n = 13), antithrombin (n = 8) and HCII (n = 1), increased Lp(a) (n = 13), and once each with elevated levels of F.II, moderate hyperhomocysteinemia, fibrinogen concentrations > 700 mg/dl and increased HRGP. In addition to the association with FV:Q506, heterozygous protein C type I deficiency was combined with deficiencies of protein S (n = 2), antithrombin (n = 1), and increased Lp(a) (n = 3). One patient showed protein C deficiency along with familially increased von Willebrand factor > 250%. Besides coexistence with FV:Q506 and protein C deficiency, protein S deficiency was combined with decreased F.XII and increased Lp(a) in one subject each. Furthermore, we found combinations of antithrombin deficiency/elevated Lp(a), hyperhomocysteinemia/Lp(a), deficiency of HCII/plasminogen, and plasminogen deficiency along with increased Lp(a) each in one. Increased prothrombin levels were associated with fibrinogen concentrations > 700 mg/dl and with HCII deficiency in one child each. Carrier frequencies of single and combined defects were significantly higher in patients compared with the controls. CONCLUSION: In conclusion, data of this multicentre evaluation indicate that paediatric thromboembolism should be viewed as a multifactorial disorder.

Adolescent↗