Search results for " Heterogeneity"

Frequency-dependent selection in human immunodeficiency virus type 1.

2001

Genetic variation is the main evolutionary strategy adopted by RNA viruses and retroviruses. Evolution operates through competition between different individuals in the same environment, resulting in the imposition of the fittest variant. The process of competition could be affected by various factors, including the frequency of the different competing individuals. In order to investigate this aspect, individual virus populations derived from a human immunodeficiency virus type 1 isolate were studied at different competing proportions. The dynamics of variant imposition in each competition experiment permitted the detection of frequency-dependent selection (FDS); i.e. the imposition of vari…

Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia

2013

Anophthalmia and microphthalmia (AM) are the most severe malformations of the eye, corresponding respectively to reduced size or absent ocular globe. Wide genetic heterogeneity has been reported and different genes have been demonstrated to be causative of syndromic and non-syndromic forms of AM. We screened seven AM genes [GDF6 (growth differentiation factor 6), FOXE3 (forkhead box E3), OTX2 (orthodenticle protein homolog 2), PAX6 (paired box 6), RAX (retina and anterior neural fold homeobox), SOX2 (SRY sex determining region Y-box 2), and VSX2 (visual system homeobox 2 gene)] in a cohort of 150 patients with isolated or syndromic AM. The causative genetic defect was identified in 21% of t…

Complement component C3: molecular basis of the C3*S025 variant and evidence for molecular heterogeneity of other variants.

1995

Complement component 3 (C3) is the central molecule of the complement system. It displays a number of polymorphic variants with, as yet, unclear functional consequences. We have investigated a number of rare C3 variants by PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis and could identify the molecular basis of a C3*S025 variant. The decreased electrophoretic mobility of this protein is caused by the exchange of a neutral serine residue to an arginine residue (positively charged). This exchange is unlikely to have functional consequences as it maps to the C-terminus of the alpha-chain. C3 variants appear to have originated from various independent mutat…

Genetic Heterogeneity and Phenotype Variation of Schizophrenia

1995

It is well proven that the manifestation of schizophrenia is under genetic control (Kendler and Diehl 1993). It is however less clear: 1. How relevant environmental factors are, and how they operate and interact with genetic factors. 2. If the genetic susceptibility is identical across the total population of schizophrenics (or at least across all subjects with familial schizophrenia), or if the specific genetic components vary across families. 3. What is transmitted in families of schizophrenics and how co-familial traits are related to genetic and genetic risk factors; are only disorders and symptoms that belong to the schizophrenic sepctrum transmitted or are neurophysiological, neuropsy…

Genetic and phenotypic heterogeneity in two novel cases of Waardenburg syndrome type IV.

2009

The STR252-IVS10nt546-VNTR7 phenylalanine hydroxylase minihaplotype in five Mediterranean samples.

1997

IVS10nt546 (IVS10nt-11g→a) is the most common molecular defect of the phenylalanine hydroxylase gene causing phenylketonuria in Mediterranean populations. Previous studies have proposed various and alternative hypotheses concerning the geographical origin and pattern of diffusion of this mutation in this area. In this study, this issue was re-examined on a large sample (149) of “Mediterranean” IVS10nt546 mutant alleles analysed with multiallelic intragenic polymorphisms. The analysis of intragenic microsatellite (STR) and minisatellite (VNTR) polymorphisms shows allelic heterogeneity of the IVS10nt546 mutation. Eight STR and three VNTR alleles were found in association with the splicing def…

Is group selection a factor modulating the virulence of RNA viruses?

1997

RNA viruses consist of populations of extremely high genetic heterogeneity called quasispecies. Based on theoretical considerations, it has been suggested that the unit of selection in such complex genetic populations is not the single viral particle but a set of genetically related particles which form the quasispecies. In the present study we carried out a set of experiments with the vesicular stomatitis virus (VSV) dealing with the evolution of life-history characters under selection acting at two factors either in the same or in opposite directions. The two factors at which selective pressure is applied are the individual and the group. We show evidence that group selection modulates th…

Wolcott-Rallison Syndrome

2004

Wolcott-Rallison syndrome (WRS) is a rare autosomal-recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other variable multisystemic clinical manifestations. Based on genetic studies of two inbred families, we previously identified the gene responsible for this disorder as EIF2AK3, the pancreatic eukaryotic initiation factor 2α (eIF2α) kinase. Here, we have studied 12 families with WRS, totalling 18 cases. With the exception of one case, all patients carried EIF2AK3 mutations resulting in truncated or missense versions of the protein. Exclusion of EIF2AK3 mutations in…

Mutations in Myosin VIIA (MYO7A) and Usherin (USH2A) in Spanish patients with usher syndrome types I and II, respectively

2002

Usher syndrome is an autosomal recessive disorder characterized by congenital hearing impairment and retinitis pigmentosa. Three clinical types are known (USH1, USH2 and USH3), and there is an extensive genetic heterogeneity, with at least ten genes implicated. The most frequently mutated genes are MYO7A, which causes USH1B, and usherin, which causes USH2A. We carried out a mutation analysis of these two genes in the Spanish population. Analysis of the MYO7A gene in patients from 30 USH1 families and sporadic cases identified 32% of disease alleles, with mutation Q821X being the most frequent. Most of the remaining variants are private mutations. With regard to USH2, mutation 2299delG was d…

Rare variants in the genetic background modulate the expressivity of neurodevelopmental disorders

2018

AbstractPurposeTo assess the contribution of rare variants in the genetic background towards variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive mutations.MethodsWe analyzed quantitative clinical information, exome-sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated mutations.ResultsThe number of rare secondary mutations in functionally intolerant genes (second-hits) correlated with the expressivity of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in probands with autism carrying gene-disruptive mutations (n=184, p=0.03) compared to …