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C Jodice

Publications and source records attributed to C Jodice.

29 records · Page 2Linked to original sources
PubMed1995

Allele and haplotype frequency distribution of the EcoRI, RsaI, and MspI COL1A2 RFLPs among various human populations.

The EcoRI, RsaI, and MspI RFLPs (restriction fragment length polymorphisms) of the COL1A2 gene, one of the two genes that encode for the polypeptides of type I collagen, have been studied in four West African and two Asian populations to evaluate their potential effectiveness as anthropological markers. All three RFLPs were in Hardy-Weinberg equilibrium. The comparisons between present data on two of the major human groups and those on Europeans and Amerindians show a considerable heterogeneity for each of the three RFLPs under study. EcoRI, in particular, appears to be highly effective in distinguishing Africans, Europeans, and Asians from each other. As expected, the analysis at the haplotype level considerably improves the discriminating efficiency of these three markers by creating a clear-cut distinction between Tharus and Indonesians, the two Asian populations of the present survey. In fact, even though these two populations exhibit the same frequencies for the RsaI and MspI alleles, the frequency of the MspI(-) allele among the RsaI(-) chromosomes is 0.5 +/- 0.14 in the Indonesian sample and 0 + 0.04 in the Tharu sample.

Base Sequence↗
PubMed1994

The trinucleotide repeat expansion on chromosome 6p (SCA1) in autosomal dominant cerebellar ataxias.

Affected members of 73 families with a variety of autosomal dominant late onset cerebellar ataxias (ADCAs) were investigated for the trinucleotide (CAG) repeat expansion which is found in pedigrees exhibiting linkage to the SCA1 locus on chromosome 6. Most of the families were too small for linkage analysis. The mutation was only found in ADCA type I, in 19 out of 38 such kindreds investigated (50%). It was slightly more common in Italian (59%) than British (50%) families, and was also found in Malaysian, Bangladeshi and Jamaican kindreds. Overall, ADCA type I patients with the expansion had a lower incidence of hyporeflexia and facial fasciculation than those without. The trinucleotide expansion was not found in eight families with ADCA and maculopathy or 24 kindreds with a pure type of ADCA, confirming that these syndromes are genetically distinct. It was also not detected in 12 patients with sporadic degenerative ataxias. DNA analysis for the SCA1 mutation is useful diagnostically in single patients or small families, and can be used for presymptomatic testing where appropriate.

Adolescent↗
PubMed1994

Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia I.

Trinucleotide repeat expansion has been found in 64 subjects from 19 families: 57 patients with SCA1 and 7 subjects predicted, by haplotype analysis, to carry the mutation. Comparison with a large set of normal chromosomes shows two distinct distributions, with a much wider variation among expanded chromosomes. The sex of transmitting parent plays a major role in the size distribution of expanded alleles, those with > 54 repeats being transmitted by affected fathers exclusively. Our data suggest that alleles with > 54 repeats have a reduced chance of survival; these appear to be replaced in each generation by further expansion of alleles in the low- to medium-expanded repeat range, preferentially in male transmissions. Detailed clinical follow-up of a subset of our patients demonstrates significant relationships between increasing repeat number on expanded chromosomes and earlier age at onset, faster progression of the disease, and earlier age at death.

Adult↗
PubMed1993

The gene for spinal cerebellar ataxia 1 (SCA1) is flanked by two closely linked highly polymorphic microsatellite loci.

The gene for one form of autosomal dominant spinal cerebellar ataxia (SCA1), is mapped by linkage to chromosome 6p, very close to the microsatellite locus D6S89. Eight large Italian kindreds segregating SCA1, as defined by very close linkage to D6S89, were genotyped with five microsatellite markers linked closely to D6S89, all mapping within a 6 cM interval on 6p. Multipoint linkage analysis and haplotypes from recombinants map SCA1 between two of these markers, D6S274 and D6S259, 5-6 cM apart. A single rare four marker haplotype within this interval shows linkage disequilibrium with the disease locus in southern Italy and is transmitted with SCA1 in five kindreds originating from this area.

Alleles↗
PubMed1993

The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps centromeric to D6S89 and shows no recombination, in nine large kindreds, with a dinucleotide repeat at the AM10 locus.

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant disorder which is genetically linked to the short arm of chromosome 6, telomeric to the human major histocompatibility complex (HLA) and very close to D6S89. Previous multipoint linkage analysis using HLA, D6S89, and SCA1 suggested that SCA1 maps centromeric to D6S89. Data from this study using nine large kindreds indicate a maximum lod score between SCA1 and D6S89 of 67.58 at a maximum recombination fraction of .004. To localize SCA1 more precisely, we identified five dinucleotide polymorphisms near D6S89. Genotypic analyses at these polymorphic loci were carried out in nine multigeneration SCA1 kindreds and in the Centre d'Etude du Polymorphisme Humain reference families. A new marker, AM10GA, demonstrates no recombination with SCA1. The maximum lod score for AM10GA linkage to SCA1 is 42.14 at a recombination fraction of 0. Linkage analysis and analysis of recombination events confirm that SCA1 maps centromeric to D6S89 and establish the following order: CEN-D6S109-AM10GA/SCA1-D6S89-LR40-D6S20 2-TEL.

Adult↗
PubMed1992

Autosomal dominant pure cerebellar ataxia. Neurological and genetic study.

A family with late-onset autosomal dominant pure cerebellar ataxia was studied both neurologically and genetically. Neuroimaging and electrophysiological results were in agreement with the clinical evidence showing involvement of the cerebellar system only, even many years after onset. No atrophy of inferior olives was observed by magnetic resonance imaging, while cerebellar atrophy was extremely marked. A very slow disease progression was observed in all patients. The disease can be differentiated from autosomal dominant olivo-ponto-cerebellar atrophies, and in particular from spinocerebellar ataxia type 1 mapping on chromosome 6p, which shows an early multisystemic involvement and a more rapid progression toward inability. A genetic study of the family with the 6p DNA marker D6S89 closely linked to the spinocerebellar ataxia type 1 locus was performed. Results showed significant exclusion of a linkage between the disease and the marker within a distance of 8.5% recombination, indicating that genetic heterogeneity underlies phenotypic differences.

Adult↗
PubMed1992

Disequilibrium of multiple DNA markers on the human Y chromosome.

We characterized four DNA polymorphisms on the Y chromosomes of 123 males from five Caucasian populations. Three markers on the male specific portion of the chromosome varied appreciably in frequency among the populations. When combined, these markers define a limited number of haplotypes compared with the maximum expected on the basis of random association. The associations found in the five groups are qualitatively similar and are thus considered to be relatively stable on an evolutionary time-scale and possibly to predate the divergence of Caucasian populations. However, the haplotype frequencies varied markedly among populations, even between weakly isolated areas such as northern vs. southern Sardinia. This may indicate rapid progression towards fixation of alternative types of Y chromosomes. We also report data suggesting that the same associations no longer hold when examining a marker as close as 275 bp from the boundary of the pseudoautosomal region on the Y chromosome.

Alleles↗
PubMed1992

HLA-linked spinocerebellar ataxia: a clinical and genetic study of large Italian kindreds.

Five families with late onset autosomal dominant spinocerebellar ataxia, were studied. Linkage between the disease and HLA loci on the short arm of chromosome 6 was shown in the two largest pedigrees. Clinical study of 26 patients and neuropathological study in one are reported. The disease was characterized by cerebellar and pyramidal involvement variably associated with cranial nerve and peripheral nervous system disorders. A remarkable concordance of the main clinical features was observed in patients with similar disease duration. Comparison with previous reports of HLA-linked spinocerebellar ataxia kindreds showed differences in clinical phenotypes. Although these might be due to genetic variation, the hypothesis is suggested that the phenotype might appear more homogeneous if disease duration is taken into account.

Adult↗
PubMed1991

The gene for autosomal dominant spinocerebellar ataxia (SCA1) maps telomeric to the HLA complex and is closely linked to the D6S89 locus in three large kindreds.

We studied three large kindreds with the HLA-linked form of spinocerebellar ataxia (SCA1) in order to localize the SCA1 locus on the short arm of chromosome 6 (6p). Two loci containing highly informative dinucleotide repeat sequences were used for linkage analysis. These two loci are D6S89, which is telomeric to the HLA region, and T complex-associated testes-expressed 1 (TCTE1), centromeric to HLA. Pairwise linkage analysis of SCA1 and D6S89 revealed a maximum lod score of 5.86 in the Houston SCA1 (HSCA1) kindred and of 8.08 in the Calabrian SCA1 (SCA1) kindreds, at recombination fractions of .050 and .022, respectively. A maximum pairwise lod score of 4.54 at a recombination frequency of .100 was obtained for SCA1 and TCTE1 in the HSCA1 kindred. No evidence for linkage was detected between TCTE1 and SCA1 in the CSCA1 kindreds. Multilocus linkage analysis of SCA1, HLA, and D6S89 in all three kindreds provided strong evidence for localization of the SCA1 locus telomeric to the HLA regions. However, multilocus linkage analysis of SCA1, HLA, and TCTE1 with HSCA1 family genotypes indicated the possibility of a location of the SCA1 locus centromeric to HLA. An analysis of HSCA1 recombinants in this region of chromosome 6 revealed relatively high recombination frequencies between HLA and each of the other two markers and relatively low frequencies between the latter and SCA1, predicting that the SCA1 locus would tend to segregate away from HLA together with D6S89 or TCTE1, as found with the three-point linkage analyses for this family.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMedDate not supplied

Phenotypic effects of expanded ataxin-1 polyglutamines with interruptions in vitro.

Spinocerebellar ataxia type 1 is a neurodegenerative disease caused by expansion of an uninterrupted glutamine repeat in ataxin-1 protein. Protein aggregation and immunoreactivity to 1C2 monoclonal antibody are two distinct pathognomonic features of expanded ataxin-1, as well as of other polyglutamine disorders. Rare cases of non-affected elderly subjects carrying expanded ataxin-1 alleles were found in random population. However, in these alleles the glutamine stretch was interrupted by histidines. Due to lack of phenotype, these alleles should be considered "normal". Most importantly, occurrence of these unusual alleles provides a unique opportunity to investigate which molecular properties of expanded ataxin-1 are not coupled to polyglutamine pathogenesis. Towards this goal, we compared in vitro the immunoreactivity to 1C2 antibody and the ability to form aggregates of interrupted and uninterrupted alleles. Immunoblotting showed that expanded-interrupted ataxin-1 had an affinity to 1C2 resembling that of normal ataxin-1. On the contrary, filter assay showed that aggregation rate of expanded-interrupted ataxin-1 resembles that of expanded-uninterrupted ataxin-1. These observations indicate that affinity for 1C2 does not directly correlate with self-aggregation of ataxin-1. Moreover, self-aggregation is not directly affected by histidine interruptions. In conclusion, these results support the hypothesis that mechanisms underlying neuronal degeneration are triggered by protein misfolding rather than by protein aggregation.

Amyloidosis↗