Aspirin and acetaminophen use by pregnant women and subsequent child IQ and attention decrements

In a longitudinal prospective study of 1,529 women pregnant in 1974-1975, aspirin and acetaminophen were the two medications most frequently taken during the first half of pregnancy (46 and 41%, respectively). In a selected cohort of 421 offspring of these women, examined at 4 years of age, maternal aspirin use during the first half of pregnancy was significantly related to IQ and attention decrements in the exposed children. Multiple regression analyses were used to statistically adjust for a variety of potentially confounding factors including demographic characteristics, child characteristics, other exposures, and lifestyle/environmental variables. Continuous dose-response and step-function parameterizations of aspirin exposure were both statistically significant and not clearly distinguishable from each other. The estimated aspirin effect is significantly greater for girls than boys. Aspirin effects on offspring function were found in the absence of effects on physical size both at birth and at 4 years. Maternal acetaminophen use was not significantly related to child IQ or attention. As this exploratory research originated from observations of a data set gathered for other purposes, it would be desirable to have these findings replicated in other studies. Further follow-up of the children at a later age is planned.     

Genetic heterogeneity in tuberous sclerosis

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by widespread hamartosis. Preliminary evidence of linkage between the TSC locus and markers on chromosome 9q34 was established, but subsequently disputed. More recently, a putative TSC locus on chromosome 11 has been suggested and genetic heterogeneity seems likely. Here we describe an approach combining multipoint linkage analysis and heterogeneity tests that has enabled us to obtain significant evidence for locus heterogeneity after studying a relatively small number of families. Our results support a model with two different loci independently causing the disease. One locus (TSC1) maps in the vicinity of the Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23.     

Structural organization of the beta-globin locus of B-haplotype sheep

Goats and some sheep synthesize a juvenile hemoglobin, Hb C (alpha 2 beta C2), at birth and produce this hemoglobin exclusively during severe anemia. Sheep that synthesize this juvenile hemoglobin are of the A haplotype. Other sheep, belonging to a separate group, the B haplotype, do not synthesize hemoglobin C and during anemia continue to produce their adult hemoglobin. To understand the basis for this difference we have determined the structural organization of the beta- globin locus of B-type sheep by constructing and isolating overlapping genomic clones. These clones have allowed us to establish the linkage map 5' epsilon I-epsilon II-psi beta I-beta B-epsilon III-epsilon IV- psi beta II-beta F3' in this haplotype. Thus, B sheep lack four genes, including the BC gene, and have only eight genes, compared with the 12 found in the goat globin locus. The goat beta-globin locus is as follows: 5' epsilon I-epsilon II-psi beta X-beta C-epsilon III-epsilon IV-psi beta Z-beta A-epsilon V-epsilon VI-psi beta Y-beta F3'. Southern blot analysis of A-type sheep reveals that these animals have a beta- globin locus similar to that of goat, i.e., 12 globin genes. Thus, the beta-globin locus of B-haplotype sheep resembles that of cows and may have retained the duplicated locus of the ancestor of cows and sheep. Alternatively, the B-sheep locus arrangement may be the result of a deletion of a four-gene set from the triplicated locus.