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M Pierluigi

Publications and source records attributed to M Pierluigi.

33 records · Page 2Linked to original sources
PubMed1992

Identification and purification of overlapping cosmid clones of the region Xq24-qter of human X chromosome using HPLC.

The assembly of a large physical map of genomes requires simultaneous analysis of many cosmid clones for overlapping regions. The search for overlapping regions may be achieved by various means. High-performance liquid chromatography (HPLC) provides an alternative to gel electrophoresis since microgram amounts of each DNA fragment may be collected into individual test tubes for further analysis. HPLC has been used to identify overlapping cosmid clones from a pool of cosmid DNA containing the terminal portion of the long arm of the human X chromosome (Xq24-qter). Among 400 cosmids analyzed, 3 were shown to overlap.

Chromatography, High Pressure Liquid↗
PubMed1991

Premutation for the Martin-Bell syndrome analyzed in a large pedigree segregating also for G6PD-deficiency. I: A working hypothesis on the nature of the FRAX-mutations.

A large Sardinian family including 13 Martin-Bell syndrome (MBS) patients, several instances of normal transmitting males or females, and the G6PD-Mediterranean mutant segregating in some of its branches, has been thoroughly investigated with the hope of gaining further insight on the nature of the FRAX-mutation. All the MBS patients and the 15 obligate heterozygous women present in the pedigree could be traced back through their X-chromosome lineage to the same ancestress, who must have been heterozygous for a silent premutation at the FRAX-locus. This premutation appears to have turned into a true FRAX-mutation at least 9 times during the gametogenesis of the ancestress' X-related descendants of whom four are males. This finding alone suggests that the transition from the FRAX premutation to the true mutation can be the result of intra- as well as interchromosomal events. This conclusion is supported by the additional observation that the genetic phase between the FRAX and the G6PD loci remained unaltered when the transition occurred in a repulsion double heterozygote for the premutation and the G6PD-Mediterranean mutant. The data described are compatible with the hypothesis that MBS patients and normal transmitting males are, respectively, hemizygous for deletion or duplication products generated by aberrant recombination events at a highly recombinogenic site of the region Xq27-Xqter. The overall message stemming from this report is that no firm conclusion can be drawn on the genetic linkage between the FRAX-locus and other markers of this region until the nature of the FRAX-mutations and the mechanism of their occurrence are fully understood.

Adult↗
PubMed1990

Origin of extra chromosome 21 in 343 families: cytogenetic and molecular approaches.

As the knowledge of parental origin and meiotic stage of nondisjunction is the prerequisite to evaluation of the possible etiological factors in trisomy 21, we have examined 343 families with at least one Down syndrome child. Of these, 322 were primary trisomies, including 24 mosaics, and 21 were structural rearrangements. This study was carried out by analysing chromosome 21 cytogenetic heteromorphisms and molecular RFLPs. In our study first maternal meiotic nondisjunction (75.3%) is the most common mechanism leading to primary trisomies. In the 24 mosaic cases, the most frequent error occurred at the first meiotic division (83%). The origin of structural rearrangements was maternal in 15 of 21 cases. Trisomy 21q21q was due to an isochromosome, and not to a translocation.

Chromosomes, Human, Pair 21↗
PubMed1990

Crossing over and chromosome 21 nondisjunction: a study of 60 families.

To test the hypothesis that meiotic nondisjunction may be caused by reduced chiasma frequency, hence recombination, we investigated 60 families with a trisomic child affected with Down syndrome (DS). We analyzed cytogenetic heteromorphisms (CH) and a number of restriction fragment length polymorphisms spanning regions 11.1 through 22.3 of 21q in both parents, in the DS child and, when available (21 families), in a normal sib. The parental origin and meiotic stage of nondisjunction were determined by combining the results of both CH and RFLP analysis. Crossover events were detected as switches in the parental haplotype expected in both DS and normal sibs. Available recombination frequency data were used to calculate the expected number of crossover events in nondisjoined and in normally segregating chromosomes, given the allele combination present in each family. The observed number of crossover events in normal meioses and in second-division nondisjunctions were consistent with the calculated figures. However, a significant reduction in the observed number of crossover events was found in nondisjoined chromosomes derived from errors in the first meiotic division and, in particular, in the proximal portion of 21q.

Chromosomes, Human, Pair 21↗
PubMed1990

Effect of x-rays on chromosome 21 nondisjunction.

In a series of 156 females and 149 males with a Down syndrome (DS) child, a case-control study was performed to evaluate the effect of abdominal-pelvic exposure to diagnostic x-rays prior to conception on nondisjunction (ND). Cytogenetic analysis using QFQ banding allowed unequivocal identification of ND parents as cases. Partners of ND parents were treated as control group. Odds ratio for the association of x-rays exposure and ND occurrence (stratified for sex and age) was 1.85 (borderline to significance: with a 95% confidence interval 1-3.44). Such an association appeared highly significant in older fathers and borderline to significant in younger mothers, when age groups were analyzed separately. By comparing mean parental ages at birth of the propositus, the prevalence of exposure to x-rays appeared moderately associated with aging in control parents of both sexes. Furthermore, the mean age of unexposed ND parents of paternally derived SD cases was the same as the referent population's, suggesting that age is not a risk factor for ND in the male, except for being associated with increasing exposure risk. Conversely, risk attributable to x-rays exposure in the female appears to be progressively diluted with increasing age, by strongly age-dependent high risk, presumably due to biologic factors that are not affected by environmental exposure.

Adult↗
PubMed1989

Isochromosome not translocation in trisomy 21q21q.

After primary trisomy, "de novo" 21q21q trisomy is the most frequent chromosomal aberration responsible for Down syndrome. This rearrangement is more commonly referred to as a Robertsonian translocation or centric fusion product than as an isochromosome, e.g., t(21q;21q) instead of i(21q); however, in practice, it has not so far proved possible to distinguish between these alternatives. The aim of this work was to establish which of the two alternatives is acceptable.

Adult↗
PubMed1989

Parental age and the origin of trisomy 21. A study of 302 families.

Several studies have attempted to define the role of parental age in determining the prevalence of 47, +21 according to the origin of nondisjunction. This report analyzes the original data of 197 informative families from Italy and reviews the available literature (96 families from Denmark and 201 from other countries). Mothers whose gametes showed nondisjunction are treated as cases, and those with normal meiosis as controls within each study. To utilize the data fully, maternal age at birth of a 47, +21 individual is treated as a continuous variable in a nonparametric comparison. The combined evidence indicates that nondisjunction in the female is associated with a significant age difference between cases and controls which is mostly due to errors in the second meiotic division. It may be inferred that in the general population, aging enhances nondisjunction at both first and second division in the female, while aging in the male is presumably associated mostly (or only) with first division errors. Implications and alternative models are discussed.

Abortion, Spontaneous↗
PubMed1988

High efficiency in the attribution of parental origin of non-disjunction in trisomy 21 by both cytogenetic and molecular polymorphisms.

The precise origin of the supernumerary chromosome can be defined in the majority of trisomy 21 cases. This is achieved by evaluating the chromosome 21 short arm polymorphism and analysing restriction fragment length polymorphisms (RFLPs) of multiple chromosome 21 loci. We report a study on 37 Italian families with Down's syndrome. In 35 cases (94.6%) both the parental and the meiotic stage of non-disjunction could be established. Knowledge of the origin of the extra chromosome 21 is a pre-requisite for investigations of genetic or environmental factors that may affect the meiotic process.

Down Syndrome↗
PubMedDate not supplied

[Non-radioactive in situ hybridization of alpha-satellite sequences in cytogenetic diagnosis].

Non isotopic in situ hybridization with alpha-satellite DNA probes in the cytogenetic diagnosis. Standard banding cytogenetic techniques do not always allow to define the structure and the origin of chromosome rearrangements involving the centromere region. Non-isotopic in situ hybridization of alphoid sequences has allowed to determine the origin of the centromeres in the metaphases of 5 patients referred to us for: 2 structural rearrangements involving chromosome 21, 2 structural rearrangements involving chromosome Y and 1 reciprocal translocation involving on chromosome 20 and one chromosome 15.

Abortion, Spontaneous↗