Biomedical subjects

Paola Melis

Publications and source records attributed to Paola Melis.

3 recordsLinked to original sources

PubMed2005

Browsing isolated population data.

BACKGROUND: In our studies of genetically isolated populations in a remote mountain area in the center of Sardinia (Italy), we found that 80-85% of the inhabitants of each village belong to a single huge pedigree with families strictly connected to each other through hundreds of loops. Moreover, intermarriages between villages join pedigrees of different villages through links that make family trees even more complicated. Unfortunately, none of the commonly used pedigree drawing tools are able to draw the complete pedigree, whereas it is commonly accepted that the visual representation of families is very important as it helps researchers in identifying clusters of inherited traits and genotypes. We had a representation issue that compels researchers to work with subsets extracted from the overall genealogy, causing a serious loss of information on familiar relationships. To visually explore such complex pedigrees, we developed PedNavigator, a browser for genealogical databases properly suited for genetic studies. RESULTS: The PedNavigator is useful for genealogical research due to its capacity to represent family relations between persons and to make a visual verification of the links during family history reconstruction. As for genetic studies, it is helpful to follow propagation of a specific set of genetic markers (haplotype), or to select people for linkage analysis, showing relations between various branch of a family tree of affected subjects. AVAILABILITY: PedNavigator is an application integrated into a Framework designed to handle data for human genetic studies based on the Oracle platform. To allow the use of PedNavigator also to people not owning the same required informatics infrastructure or systems, we developed PedNavigator Lite with mainly the same features of the integrated one, based on MySQL database server. This version is free for academic users, and it is available for download from our site http://www.shardna.com.

Algorithms↗

PubMed2003

Identification of a novel gene and a common variant associated with uric acid nephrolithiasis in a Sardinian genetic isolate.

Uric acid nephrolithiasis (UAN) is a common disease with an established genetic component that presents a complex mode of inheritance. While studying an ancient founder population in Talana, a village in Sardinia, we recently identified a susceptibility locus of approximately 2.5 cM for UAN on 10q21-q22 in a relatively small sample that was carefully selected through genealogical information. To refine the critical region and to identify the susceptibility gene, we extended our analysis to severely affected subjects from the same village. We confirm the involvement of this region in UAN through identical-by-descent sharing and autozygosity mapping, and we refine the critical region to an interval of approximately 67 kb associated with UAN by linkage-disequilibrium mapping. After inspecting the genomic sequences available in public databases, we determined that a novel gene overlaps this interval. This gene is divided into 15 exons, spanning a region of approximately 300 kb and generating at least four different proteins (407, 333, 462, and 216 amino acids). Interestingly, the last isoform was completely included in the 67-kb associated interval. Computer-assisted analysis of this isoform revealed at least one membrane-spanning domain and several N- and O-glycosylation consensus sites at N-termini, suggesting that it could be an integral membrane protein. Mutational analysis shows that a coding nucleotide variant (Ala62Thr), causing a missense in exon 12, is in strong association with UAN (P=.0051). Moreover, Ala62Thr modifies predicted protein secondary structure, suggesting that it may have a role in UAN etiology. The present study underscores the value of our small, genealogically well-characterized, isolated population as a model for the identification of susceptibility genes underlying complex diseases. Indeed, using a relatively small sample of affected and unaffected subjects, we identified a candidate gene for multifactorial UAN.

Amino Acid Sequence↗

PubMed2003

Urinary glycosaminoglycans as risk factors for uric acid nephrolithiasis: case control study in a Sardinian genetic isolate.

OBJECTIVES: To assess the clinical association between glycosaminoglycan (GAG) excretion and uric acid (UA) nephrolithiasis by measuring urinary GAG levels in a case-control study conducted in a Sardinian genetic isolate. Inhibitors of crystallization such as GAGs seem to be involved in kidney stone formation. METHODS: Overnight (12-hour) urinary excretion of GAGs, calcium, oxalate, and UA were measured in urine samples from 60 patients who had formed at least one urinary stone (UA or mixed) and 52 healthy controls. The total GAG concentration was measured by a dye-binding assay, and the values were normalized against creatinine to obtain values in micrograms of GAG per milligram creatinine. Statistical analysis was performed using t tests and logistic regression analysis. RESULTS: No significant difference was found between the two groups with respect to calcium and oxalate concentrations. Nonetheless, stone formers had significantly lower levels of GAGs (29.5 +/- 2.2 versus 36.4 +/- 3.9 microg/mg creatinine, P = 0.003) and greater levels of UA (385.11 +/- 38.2 versus 298.43 +/- 31.4 mg/12 hr, P = 0.0010) than did the normal controls. CONCLUSIONS: We report that the lower excretion of GAGs in stone formers could impair their inhibitory activity on UA stone formation, and, as a consequence, it may represent a risk factor for this form of urolithiasis.

Case-Control Studies↗