Biomedical subjects

S R Matioli

Publications and source records attributed to S R Matioli.

9 recordsLinked to original sources

PubMed2004

Asymptomatic carriers and gender differences in facioscapulohumeral muscular dystrophy (FSHD).

Facioscapulohumeral muscular dystrophy is an autosomal dominant muscle disorder, mapped to 4q35. It is characterized by remarkable inter- and intrafamilial clinical variability ranging from severe phenotype to asymptomatic carriers. The aim of the present study was to assess the size of the Eco RI fragment in a large sample of asymptomatic or minimally affected carriers as well as symptomatic patients, comparing both sexes, in order to verify if asymptomatic carriers are randomly distributed or concentrated in some particular families and if there is preferential parental transmission (maternal or paternal) resulting in non-penetrant carriers. We have analysed a total of 506 individuals from 106 unrelated families with at least one affected facioscapulohumeral muscular dystrophy proband. In all patients the molecular diagnosis was confirmed following double digestion (Eco RI/Bln I fragment <35 kb). About 20% among probands' relatives who were found to carry the small fragment were asymptomatic or minimally affected, without preferential parental transmission, but with a significantly higher proportion of females (n=37) than males (n=14). Although asymptomatic carriers were found in about 30% of the families, some genealogies seem to concentrate more non-penetrant cases. A significant correlation between the size of the Eco RI fragment and severity of the phenotype was observed in the total sample but surprisingly this correlation is significant only among affected females. The gender difference in clinical manifestation as well as the observation that asymptomatic carriers are not rare should be taken into consideration in genetic counseling of affected patients or 'at-risk' relatives.

Adult↗

PubMed2004

Epistasis affecting litter size in mice.

Litter size is an important reproductive trait as it makes a major contribution to fitness. Generally, traits closely related to fitness show low heritability perhaps because of the corrosive effects of directional natural selection on the additive genetic variance. Nonetheless, low heritability does not imply, necessarily, a complete absence of genetic variation because genetic interactions (epistasis and dominance) contribute to variation in traits displaying strong heterosis in crosses, such as litter size. In our study, we investigated the genetic architecture of litter size in 166 females from an F2 intercross of the SM/J and LG/J inbred mouse strains. Litter size had a low heritability (h2 = 12%) and a low repeatability (r = 33%). Using interval-mapping methods, we located two quantitative trait loci (QTL) affecting litter size at locations D7Mit21 + 0 cM and D12Mit6 + 8 cM, on chromosomes 7 and 12 respectively. These QTL accounted for 12.6% of the variance in litter size. In a two-way genome-wide epistasis scan we found eight QTL interacting epistatically involving chromosomes 2, 4, 5, 11, 14, 15 and 18. Taken together, the QTL and their interactions explain nearly 49% (39.5% adjusted multiple r2) of the phenotypic variation for litter size in this cross, an increase of 36% over the direct effects of the QTL. This indicates the importance of epistasis as a component of the genetic architecture of litter size and fitness in our intercross population.

Animals↗

PubMed2002

Evidence that BCL3 plays a role in the etiology of nonsyndromic oral clefts in Brazilian families.

The BCL3 gene has been considered a susceptibility locus for nonsyndromic cleft lip with or without cleft palate (NSCL/P), based on association and linkage studies in some populations. We evaluated an intragenic marker at the BCL3 gene and the microsatellite D19S178 (1.1 cM distant from the BCL3 gene) among 98 infants born with NSCL/P and their parents, using the transmission disequilibrium test (TDT) and a method for haplotype analysis. Our analysis, based on BCL3 alleles, revealed the existence of a marginal association of allele 135pb of the BCL3 gene with NSCL/P (chi(2)=3.60; P=0.058; 1 df), with a major effect in female (chi(2)=5.77; P=0.016; 1 df) and in familial cases (chi(2)=3.79; P=0.051; 1 df). However, the haplotype analysis detected no significant segregation distortion, even if the alleles of the D19S178 were grouped into two classes. These findings support previous findings that BCL3 plays a role in the etiology of NSCL/P as an allele of low penetrance or as a modifier locus. We hypothesize that there might be more than one mutation in this gene associated with NSCL/P, or alternatively, that more than one mutation has arisen associated with the 135-bp allele. Genet. Epidemiol. 23:364-374, 2002

Alleles↗

PubMed2001

No evidence of association between the D10S1423 locus and Alzheimer disease in Brazilian patients.

In a genome survey for Alzheimer's disease (AD), Zubenko et al. (1998) reported that the 234bp allele of the D10S1423 locus was more frequent among AD cases than in controls. We have analyzed this polymorphic locus in patients and healthy controls and observed that the 226bp allele is the most frequent allele in the D10S1423 locus in Brazilian AD patients. However, no statistically significant association between any D10S1423 allele was observed in AD patients as well as in controls.

Aged↗

PubMed2000

Analysis of the disease risk locus DXS1047 polymorphism in Brazilian Alzheimer patients.

Alzheimer's disease (AD) is a disorder characterized by a progressive deterioration in memory and other cognitive functions. Four genes associated with early onset AD have been identified but familial AD is rare. The majority of late onset AD (LOAD) is caused by a complex inheritance with several genes interacting with environmental factors. The epsilon4 allele of the apolipoprotein E (APOE) gene has been reported worldwide as a risk factor associated with LOAD. The short variant of a polymorphism in the transcriptional region of the serotonin transporter gene (5-HTTLPR) was analyzed in several psychiatric conditions and found to be more frequently associated with European and Brazilian LOAD patients. Recently, allelic associations with LOAD were reported for five other loci, the most significant for one X-linked 202-bp allele, at the DXS1047 locus. We have analyzed this locus in Brazilian LOAD patients and observed that the 202-bp allele was not significantly more frequent among patients. In contrast, two other alleles (200 bp and 208 bp) were less frequent among AD male patients than in controls, confirming the importance of replicating association studies in different populations.

Age of Onset↗

PubMed1999

Coadapted gene complexes for morphological traits in Drosophila mercatorum. Two-loci interactions.

The availability of molecular and morphological markers in a parthenogenetically reproducing strain of Drosophila mercatorum allowed us to design an experiment in which we could obtain a sample of completely homozygous recombinant females from two different parental homozygous strains. The phenotypic values of body-size-related measures and bristle numbers (sternopleural and abdominal) were measured in females sampled from the parental, F1 and F2 generations. The DNA extracted from the F2 flies was scored for five Mendelian segregating loci through double stringency PCR. In addition, the flies were scored for three morphological recessive loci. We estimated all single-locus and all two-loci associations between the marker loci with the principal components of the morphological data, which allowed us also to estimate the epistatic parameters. The results suggest that the underlying genetic architecture of the morphological phenotypes cannot be regarded as a result of additivity only, but instead, involves many different kinds of interactions that are distributed around an additive mean.

Animals↗

PubMed1995

Obtaining genetic markers by using double-stringency PCR with microsatellites and arbitrary primers.

A technique to obtain genetic markers is described. PCR is performed at two different annealing temperatures in a single reaction mixture. During the first cycles, a single microsatellite oligonucleotide is used as primer to amplify DNA between two microsatellite regions. The annealing temperature and consequent stringency is then lowered, and in further cycles a random-amplified polymorphic DNA (RAPD) primer exponentially amplifies parts of the previously amplified fragments, which contain sequences complementary to the RAPD primer. The first round of specific amplification is found to be crucial for obtaining consistent, repeatable results, as compared with the results obtained by RAPD alone. This technique was proven to produce genetically informative markers, as revealed by crosses performed with Drosophila mercatorum strains, and it can be used for genetic mapping or population genetics studies.

Animals↗

PubMed1986

Genetical and biochemical comparisons of alcohol dehydrogenase isozymes from Anastrepha fraterculus and A. obliqua (Diptera: Tephritidae): evidence for gene duplication.

The electrophoretic patterns of the enzyme alcohol dehydrogenase (ADH) from Anastrepha fraterculus and A. obliqua were studied. Two loci were found to code for the enzyme in A. fraterculus, and three in A. obliqua. In both species, all isozymes were active in third-instar larvae. A cationic isozyme (Adh-1) was active mainly in the visceral fat body of both species. In A. fraterculus, the locus had an anionic polymorphic isozyme (Adh-3) that was detected in the parietal fat body. In addition to these two loci, a third locus for an anionic isozyme (Adh-2), which was active in the digestive tube of larvae, was present in A. obliqua and probably resulted from gene duplication. For both species, multiple forms of the isozymes are formed by binding of an NAD-carbonyl compound, as in Drosophila melanogaster. Both larvae and early pupae of A. obliqua had almost twice the specific ADH activity as A. fraterculus. The ethanol content of the host fruit infested with A. obliqua (red "mombim") was also higher than that of the host fruit infested with A. fraterculus (guava).

Alcohol Dehydrogenase↗

PubMedDate not supplied

Molecular adaptation of Drosophila melanogaster lysozymes to a digestive function.

A lysozyme (pI 5.5) was purified to homogeneity from heated acid extracts of Drosophila melanogaster larvae, using gel filtration in a Superose column and ion-exchange chromatography in a Mono Q column. The final yield was 67%. The purified lysozyme with Mr 13,700 (determined by SDS-polyacrylamide gel electrophoresis) decreases in activity and has its pH optimum displaced towards acidic values and Km increases as the ionic strength of the medium becomes higher. The lysozyme is resistant to a cathepsin D-like proteinase present in cyclorrhaphous Diptera and displays a chitinase activity which is 11-fold higher than that of chicken lysozyme. Microsequencing of an internal peptide of the purified lysozyme showed that this enzyme is the product of the previously sequenced Lys D gene. The results suggest that the product of the Lys P gene has pI 7.2, a pH optimum around 5 and is not a true digestive enzyme. The most remarkable sequence convergence of D. melanogaster lysozyme D and lysozymes from vertebrate foregut fermenters are serine 104 and a decrease in the number of basic amino acids, suggesting that these features are necessary for digestive function in an acid environment. Adaptive residues putatively conferring stability in an acid proteolytic environment differ between insects and vertebrates, probably because they depend on the overall three-dimensional structure of the lysozymes. A maximum likelihood phylogeny and inferences from insect lysozyme sequences showed that the recruitment of lysozymes as digestive enzymes is an ancestral condition of the flies (Diptera: Cyclorrhapha).

Adaptation, Physiological↗