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Human chromosomes were labeled with base-specific radioactive DNA precursors and examined autoradiographically to measure their DNA content and base ratio (percentage A-T base pairs). The requirement that incorporation of labeled bases be uniform during DNA synthesis was met by the use of inhibitors of de novo synthesis of DNA precursors. The genome was subdivided into 75 segments based on quinacrine banding, and the base ratio of each was calculated by a method that corrects for bias due to the scatter of grains about their source. Estimates of base ratio are shown to be sufficiently precise to detect variability among chromosomes and among segments within a chromosome. Analysis of these data and of measurements of the quinacrine fluorescence intensity of segments leads to the following conclusions. Base ratio is positively correlated with brightness, as predicted from independent in vitro studies. Larger chromosomes tend to have higher base ratios and to be brighter than smaller ones. The best prediction of the brightness of a segment must take into account not only its base ratio but also its DNA content. To explain these results, we suggest an evolutionary model in which chromosomes containing repeated sequences of A-T-rich DNA tend to grow by means of unequal sister chromatid and meiotic exchanges.

The Alzheimer amyloid protein precursor (APP) has previously been localized to human chromosome 21q11.2–q21. We have refined the regional localization to a small region including chromosome bands 21q21.105–q21.05 by using quantitative Southern blot analysis of cell lines aneuploid for parts of chromosome 21. Our findings exclude the APP gene from the minimal region producing the classical phenotypic features of Down syndrome. This further narrowing of the APP location will help in identifying the physical location of the gene causing familial Alzheimer disease.

Sister chromatid exchanges are sharply demarcated in Giemsa stained metaphase preparations of Chinese hamster ovary cells and human peripheral leukocytes. Chromatids singly and doubly substituted with BrdU acquire differential Giemsa stain affinities after treatment at 88° C for 10 minutes in 1.0 M Na phosphate buffer (pH 8.0).

An improved technique for cultivation of peripheral human lymphocytes is presented. The settling of the blood cells is replaced by a wash in Ficoll to remove the polymorphonucleocytes.

Central hypoventilation syndrome may be congenital or appear later in life. At least two heritable forms have been reported. We have previously documented central alveolar hypoventilation in association with pyruvate dehydrogenase complex deficiency. In addition, a syndrome including congenital central hypoventilation, Hirschsprung's megacolon and disturbance of esophageal motility has been described in two infant sisters and an unrelated boy. We herein report congenital central hypoventilation in both a 4½ month old girl and her (deceased) 3½ month old brother. Almitrine, a peripheral chemoreceptor stimulant, did not affect respiration in the former. While the girl also manifested disturbed esophageal motility and Hirschsprung's disease, pre- and post-mortem histologic study of the large and small intestine revealed no abnormalities of ganglion cells. We conclude that the aggregate data support autosomal recessive inheritance for this syndrome. Further, the syndrome manifestations are variable in their expressivity, and the disorder—with its attendant 25% recurrence risk—must certainly be considered in babies with congenital central hypoventilation.