Showing papers by "Nancy L. Saccone published in 2002"

Defining alcohol-related phenotypes in humans. The Collaborative Study on the Genetics of Alcoholism.

Abstract: Alcoholism is a disease that runs in families and results at least in part from genetic risk factors. The Collaborative Study on the Genetics of Alcoholism (COGA) is a Federally funded effort to identify and characterize those genetic factors. The study involves more than 1,000 alcoholic subjects and their families, with researchers conducting comprehensive psychological, physiological, electrophysiological, and genetic analyses of the participants. These analyses have identified several traits, or phenotypes, that appear to be genetically determined, such as the presence of alcohol dependence, the level of response to alcohol, the presence of coexisting depression, or the maximum number of drinks a person consumes per occasion. Genetic analyses have identified regions on several chromosomes that are associated with these phenotypes and need to be studied further.

A multi-incident, Old-Order Amish family with PD

Abstract: Background: PD is largely a sporadic condition of unknown etiology, but specific inherited mutations are a cause of PD. Objective: To describe a large, multi-incident Amish pedigree with PD. Methods: Case ascertainment, calculation of population prevalence, and calculation of kinship coefficients (a measure of relatedness between two individuals) for affecteds and subjects in a large kindred with PD were conducted. Sequencing of genes with known mutations sufficient to cause PD and marker-by-marker haplotype analysis in chromosomal regions flanking previously described genes with known mutations were performed. Results: The authors have examined 113 members of this pedigree and classified 67 as normal (no evidence of PD), 17 as clinically definite PD, 6 as clinically probable PD, and 23 as clinically possible PD. The mean age at onset of the clinically definite subjects was 56.7 years. The phenotype in this family is typical of idiopathic PD, including rest tremor, rigidity, bradykinesia, postural instability, and response to levodopa. In addition, dementia occurred in six of the clinically definite subjects, and many subjects experienced levodopa-related motor complications including wearing off and dopa-induced dyskinesias. In the index Amish community, a minimum prevalence of PD in the population 40 years and older of 552/100,000 was calculated. The mean kinship coefficient in the subjects with PD and those with PD by history (0.036) was higher ( p = 0.007) than in a group of age-matched normal Amish control subjects (0.016), providing evidence that PD is inherited in this family. Sequence analysis did not detect any mutations in known PD genes. No single haplotype cosegregates with the disease in any of the chromosomal regions previously found to be linked to PD, and no marker in these regions exhibits increased homozygosity among definite PD cases. Conclusions: PD in this community is more common than in the general population, and this increased prevalence may be due in part to a novel gene(s).

Linkage for platelet monoamine oxidase (MAO) activity: results from a replication sample.

Abstract: Background: Monoamine oxidase B (MAO-B) degrades catecholamines in presynaptic nerve endings and is also active in platelets. There is evidence to suggest that platelet MAO-B activity level is controlled by a major genetic locus distinct from the structural gene on the X chromosome. To expand on a prior report, new linkage analyses for platelet MAO-B activity have been performed on the previously analyzed sample (designated the initial sample), on a new sample of families (the replication sample), and on the combined sample. These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Methods: The initial sample consists of 105 extended families providing 1002 nonindependent (412 independent) sib pairs that have been phenotyped for MAO activity and genotyped. The replication sample of 157 extended families contains 608 nonindependent (309 independent) phenotyped and genotyped sib pairs. Analyses were conducted using Haseman-Elston based regression on sib pairs and variance component analysis on extended pedigrees, and the importance of cigarette smoking and gender as covariates of platelet MAO-B activity was taken into account. Results: Regions on chromosomes 2, 9, and 12 indicated consistent evidence for linkage across the two distinct datasets by at least one analysis method. Under Haseman-Elston regression of independent sib pairs, only the chromosome 2 region gave lod scores above 1 in both the initial and replication samples. Using all possible pairs, unweighted, for the regression, chromosome 12 gave lod scores above 1 in both samples. For variance component analysis, only the chromosome 9 region gave lod scores above 1 in both samples. Conclusions: The consistency across datasets of these findings is encouraging. In particular, variance component analysis of extended pedigrees supports a potential linkage of MAO-B activity to chromosome 9, with a lod over 3 at 115 cM near D9S261 in the combined sample. Sib-pair regression supports this finding with modest lod scores in the region. Suggestive linkage to chromosomes 2 and 12 from sib-pair analysis is only weakly supported by variance component analysis.