[Laurence-Moon-Biedl-Bardet syndrome a in a 6-year-old girl with asthma and dysgammaglobulinemia].
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A systematic review of the 19th-century literature related to sleep disorders revealed that patients with obstructive sleep apnea were vividly described in the second half of the century. Also, there were documented observations on the linkage between airway obstructions and noisy snoring, nocturnal insomnia, and excessive somnolence. The coining of the term "pickwickian" to describe an obese somnolent patient was made in 1889 during a clinical presentation of a patient with sleep apnea. Respiratory failure in sleep because of "failure of the chest and diaphragmatic movements" was defined as a specific sleep disorder by Silas Weir Mitchell in 1890. The two main reasons for overlooking the sleep apnea syndrome for so long have been misdiagnosis of patients with sleep apnea as having narcolepsy and skepticism regarding the validity of excessive somnolence as a clinical sign.
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We develop least squares (LS) procedures for variance components estimation in genetic linkage studies. The LS procedure is expressed by simple expressions, and does not require inversion of large matrices. Simulations comparing LS with maximum likelihood (ML) procedures for normal data show that both yield unbiased estimators, but the efficiency of the LS procedure was less than 50% of the ML procedure. For bivariate normal data, the efficiency of the LS procedure relative to the ML method was better, generally over 60%. For skewed data, the LS method was markedly more efficient than ML for parameter estimation. The LS method was computationally rapid, over 4,000 times faster than ML estimation for bivariate data. Because ML estimation is time consuming, LS methods are suggested for initial interval mapping with multivariate data.
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Several research groups have begun mounting large, ambitious family studies to map genes for atherosclerosis, heart disease, and their major risk factors using whole genome linkage and/or disequilibrium scans. Some of the problems, pitfalls, and challenges of this exciting effort are examined and illustrated with lessons from an earlier mapping problem.
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