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

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

Significant Linkage of Parkinson Disease to Chromosome 2q36-37

Parkinson disease (PD) is the second most common neurodegenerative disorder, surpassed in frequency only by Alzheimer disease. Elsewhere we have reported linkage to chromosome 2q in a sample of sibling pairs with PD. We have now expanded our sample to include 150 families meeting our strictest diagnostic definition of verified PD. To further delineate the chromosome 2q linkage, we have performed analyses using only those pedigrees with the strongest family history of PD. Linkage analyses in this subset of 65 pedigrees generated a LOD score of 5.1, which was obtained using an autosomal dominant model of disease transmission. This result strongly suggests that variation in a gene on chromosome 2q36-37 contributes to PD susceptibility

Genome Screen to Identify Susceptibility Genes for Parkinson Disease in a Sample without parkin Mutations

Parkinson disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity, and postural instability, as well as by a clinically significant response to treatment with levodopa. Mutations in the α-synuclein gene have been found to result in autosomal dominant PD, and mutations in the parkin gene produce autosomal recessive juvenile-onset PD. We have studied 203 sibling pairs with PD who were evaluated by a rigorous neurological assessment based on (a) inclusion criteria consisting of clinical features highly associated with autopsy-confirmed PD and (b) exclusion criteria highly associated with other, non-PD pathological diagnoses. Families with positive LOD scores for a marker in an intron of the parkin gene were prioritized for parkin-gene testing, and mutations in the parkin gene were identified in 22 families. To reduce genetic heterogeneity, these families were not included in subsequent genome-screen analysis. Thus, a total of 160 multiplex families without evidence of a parkin mutation were used in multipoint nonparametric linkage analysis to identify PD-susceptibility genes. Two models of PD affection status were considered: model I included only those individuals with a more stringent diagnosis of verified PD (96 sibling pairs from 90 families), whereas model II included all examined individuals as affected, regardless of their final diagnostic classification (170 sibling pairs from 160 families). Under model I, the highest LOD scores were observed on chromosome X (LOD score 2.1) and on chromosome 2 (LOD score 1.9). Analyses performed with all available sibling pairs (model II) found even greater evidence of linkage to chromosome X (LOD score 2.7) and to chromosome 2 (LOD score 2.5). Evidence of linkage was also found to chromosomes 4, 5, and 13 (LOD scores >1.5). Our findings are consistent with those of other linkage studies that have reported linkage to chromosomes 5 and X

Significant Linkage of Parkinson Disease to Chromosome 2q36-37

Parkinson disease (PD) is the second most common neurodegenerative disorder, surpassed in frequency only by Alzheimer disease. Elsewhere we have reported linkage to chromosome 2q in a sample of sibling pairs with PD. We have now expanded our sample to include 150 families meeting our strictest diagnostic definition of verified PD. To further delineate the chromosome 2q linkage, we have performed analyses using only those pedigrees with the strongest family history of PD. Linkage analyses in this subset of 65 pedigrees generated a LOD score of 5.1, which was obtained using an autosomal dominant model of disease transmission. This result strongly suggests that variation in a gene on chromosome 2q36-37 contributes to PD susceptibility