Paternal transmission and anticipation in schizophrenia.
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Recent studies have observed anticipation (earlier age at onset (AAO) or increased disease severity in successive generations) in familial schizophrenia. In other disorders, where the molecular mechanism (repeat expansion) is known, anticipation varies in degree depending on the sex of the transmitting parent. We investigated parental sex effects on anticipation in schizophrenia, using a familial sample of affected two-generation pairs in which anticipation had previously been demonstrated using the median intergenerational difference (MID) in AAO. A Wilcoxon rank sum test for independent samples was used to determine whether MID in AAO was significantly different for paternal and maternal transmission. Results suggested that in a sample of 127 parent-offspring pairs, anticipation was greater with paternal than with maternal transmission (MID = 18 and 14 years, respectively, P = 0.05). Paternal effects were strongest in 39 parent-offspring pairs with early-onset offspring (< or = 21 years) (MID = 22 and 17 years, respectively, for paternal and maternal transmission, P = 0.01). However, assessment of the effect of possible selection biases suggests that preferential ascertainment of late-onset fathers may have exerted important effects. While the results support possible paternal effects, further studies are needed to draw firm conclusions about true parent-of-origin effects on anticipation in familial schizophrenia. (+info)
The Oral History Program: II. Personal views of health sciences librarianship and the Medical Library Association.
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The Medical Library Association Oral History Program uses accepted oral history techniques to collect and preserve interviews with members. The original taped interviews and transcripts are kept in the Medical Library Association archives and made available for research purposes; edited copies of the interviews are distributed through the National Network of Libraries of Medicine, and members are encouraged to borrow and read the histories. Summaries of forty-three interviews provide personal views on health sciences librarianship and the Medical Library Association. (+info)
Accuracy of DNA amplification from archival hematological slides for use in genetic biomarker studies.
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Archival slides are a potentially useful source of DNA for mutation analyses in large population-based studies. However, it is unknown whether specimen age or histological stains alter the accuracy of Taq polymerase or induce secondary mutations in sample DNA. To address this question, we evaluated five methods for extraction of genomic DNA from archival bone marrow slides of 17 leukemia patients and analyzed exons 1 and 2 of the N- and K-ras genes for the presence of mutations. Of the five methods, optimal DNA purification was achieved by boiling and phenol:chloroform extraction. N-and K-ras exons 1 and 2 were independently amplified using 35 cycles of PCR, and 6-12 clones for each exon were isolated and individually sequenced for each patient. Mutations were confirmed by repeat extraction, cloning, and sequencing. Sixteen of 17 patient samples were successfully amplified (94%), including slides up to 29 years old. Twelve slides had been stained with Wright-Giemsa, I stained with toluidine blue, and 4 were unstained. A total of 16 single-base mutations were identified of 33,840 nucleotides sequenced. No insertions or deletions were identified. Six of 16 single-base mutations were previously described activating mutations in codon 13 of N-ras exon 1. The 10 other mutations were in other regions of the N- and K-ras genes and were not reproduced after repeat extraction, cloning, and sequencing. The frequency of these other alterations was I of 3384 bp. This value is comparable with the inherent error frequency for Taq polymerase. Our findings suggest that high fidelity DNA amplification can be achieved using archival hematological slides as old as 29 years and can be reliably used in genetic analyses. (+info)