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L Giuffra

Publications and source records attributed to L Giuffra.

6 recordsLinked to original sources
PubMed1992

A genetic linkage study of schizophrenia to chromosome 5 markers in a northern Italian population.

Some recent findings report that the area 5q11.2-13.3 of chromosome 5 segregates with schizophrenia in an uncle-nephew pair (Bassett et al 1988). However, linkage studies between chromosome 5 markers loci and schizophrenia lead to different results: Sherrington et al (1988) found a positive linkage, whereas other groups of researchers found evidence against linkage (Kennedy et al 1988; St. Clair et al 1989; Detera-Wadleigh et al 1989; McGuffin et al 1990; Aschauer et al 1990; Crowe et al 1991). We have studied five Italian pedigrees segregating schizophrenia using a map of four markers for the chromosomal region 5q11.2-13.3. Linkage analyses revealed negative lod scores, and thus no evidence for linkage was obtained in our Italian families.

Chromosome Mapping↗
PubMed1992

Model misspecification and multipoint linkage analysis.

Pairwise linkage analysis is robust to genetic model misspecification provided dominance is correctly specified, the primary effect being inflation of the recombination fraction. By contrast, we show that multipoint analysis under misspecified models is not robust when a putative disease locus is placed between close flanking markers, with potentially spuriously negative multipoint lod scores being produced. The problem is due to incorrect attribution of segregation of a disease allele and the consequent conclusion of (unlikely) double crossovers between flanking markers. As a possible solution, we propose the use of high disease allele frequencies, as this allows probabilistically for nonsegregation (through parental homozygosity or dual matings). We show analytically and through analysis of pedigree data simulated under a two-locus heterogeneity model that using a disease allele frequency of 0.05 in the dominant case and 0.25 in the recessive case is quite robust in producing positive multipoint lod scores with close flanking markers across a broad range of conditions including varying allele frequencies, epistasis, genetic heterogeneity and phenocopies.

Animals↗
PubMed1991

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease.

A locus segregating with familial Alzheimer's disease (AD) has been mapped to chromosome 21, close to the amyloid precursor protein (APP) gene. Recombinants between the APP gene and the AD locus have been reported which seemed to exclude it as the site of the mutation causing familial AD. But recent genetic analysis of a large number of AD families has demonstrated that the disease is heterogeneous. Families with late-onset AD do not show linkage to chromosome 21 markers. Some families with early-onset AD show linkage to chromosome 21 markers, but some do not. This has led to the suggestion that there is non-allelic genetic heterogeneity even within early onset familial AD. To avoid the problems that heterogeneity poses for genetic analysis, we have examined the cosegregation of AD and markers along the long arm of chromosome 21 in a single family with AD confirmed by autopsy. Here we demonstrate that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene. This mutation causes an amino-acid substitution (Val----Ile) close to the carboxy terminus of the beta-amyloid peptide. Screening other cases of familial AD revealed a second unrelated family in which this variant occurs. This suggests that some cases of AD could be caused by mutations in the APP gene.

Alzheimer Disease↗