Usefulness of direct sequencing of pooled DNA for SNP identification and allele-frequency determination compatible with a common disease/common variant hypothesis.

We examined the efficiency of direct sequencing of pooled DNA for developing common single nucleotide polymorphisms (SNPs) and its accuracy for estimating allele frequencies. A pool of 200 control DNAs was established and was used for developing SNPs and estimating minor allele frequencies (MAF). The sensitivity of the pooled DNA method for successfully detecting an SNP with an MAF >0.01 listed in the database was approximately 0.7; it was particularly efficient for detecting SNPs with MAF >0.1, which is compatible with the common disease/common variant hypothesis. The mean difference between the estimated and the observed MAFs was 0.03 +/- 0.023. The pooled DNA method identified four additional SNPs, for which the allele frequency information was not available in the database. The pooled DNA method is a cost- and time-effective tool for both qualifying and quantifying SNPs with considerable accuracy, and it can be particularly useful for dissecting the common disease/common variant hypothesis; this represents a best-case scenario for large-scale association mapping.

Behçet's disease in Brazil--a review of 49 cases with emphasis on ophthalmic manifestations.

At the Uveitis Clinic of the Department of Ophthalmology of the Escola Paulista de Medicina, São Paulo, Brazil, Behçet's disease was diagnosed in 49 patients, representing 2.0% of the total uveitis cases attended during the 16-year period from February 1974 to June 1990. Of these, 71% were men. The age of onset of the disease was between 9 and 61 years, with a mean of 29.6 years. The ethnic distribution was the following: 76% Caucasian, 14% darkly pigmented, 8% Mongoloid and 2% Negroid. HLA-B5 was found in 45.5% of the 11 Caucasian patients typed. In 34.5% of the cases, the ocular attack was the initial manifestation, alone or associated with other symptoms. Oral aphthae were recorded in 98% of the patients, genital ulcers in 55.1%, and skin lesions in 51%. Joint involvement was present in 44.9%, neurologic symptoms were evidenced in 3 patients, and 2 patients had major vascular involvement. The mean interval between the first manifestation of the disease and the onset of ocular involvement was 3.1 years, with a range of 4 months to 14 years. The interval between affections of both eyes ranged from 0 to 2 years; in 38.4% of the cases it occurred within one month. Anterior and posterior segment involvement was seen in 85.7% of the patients. Hypopyon was observed in 34.7% of the cases. Seven patients did not present iridocyclitis at any time in the course of their disease. We did not see any cases with only anterior segment involvement.(ABSTRACT TRUNCATED AT 250 WORDS)