Genetic and evolutionary relationships among Asian Macaques

Published gene frequency data, checked for consistency of allele definitions across laboratories and for comparability of geographically identical samples, were pooled into a data set containing frequencies at nine loci for each of 20 populations that encompassed 10 macaque species. Genetic distances were calculated by the methods of Kidd and Cavalli-Sforza (1974). These distances were used to construct phylogenetic trees and to evaluate the relationships between divergence times and effective population sizes. Inter-and intraspecific genetic distances and the groupings defined by phenetic tree analyses support Fooden’s (1976) classification of the genus Macacainto four species groups. A paleozoogeographical model of Asia including the known times of major sea-level changes allows us to explain Macacainto four species groups. A paleozoogeographical model of Asia including the known times of major sea-level changes allows us to explain qualitatively the inferred evolutionary relationships among macaque species. Many assumptions are required in order to estimate the variables necessary in the quantitative prediction of genetic differences for a comparison between any two populations. Examination of those assumptions demonstrates the need for more accurate genetic as well as paleozoogeographic information. An erratum to this article is available at .     

Predicting genotypes at loci for autosomal recessive disorders using linked genetic markers: application to Wilson's disease

Summary Recently, the Wilson's disease locus (WND) has been mapped to the long arm of chromosome 13. We have analyzed segregation of serveral chromosome 13 markers flanking the WND locus and used multipoint linkage analysis to determine the most likely WND genotype of each of 57 unaffected individuals in 5 Wilson's disease families. Approximately 46% of these could be classified as carrier (heterozygote), homozygous normal, or homozygous affected (not yet symptomatic) with a probability of at least 90%, while 77% could be classified with a probability of at least 80%. Our results demonstrate that even though there is a significant decrease on average in serum copper concentration in Wilson's disease heterozygotes compared to normal homozygotes, other sources of variation in serum copper concentration are much greater and preclude use of serum copper to detect heterozygotes for Wilson's disease. Subsequent analyses showed that a familial component, independent of WND genotype, is the major factor accounting for variation in ceruloplasmin levels among unaffected individuals; age is another factor accounting for more variation in copper levels among unaffected individuals than WND genotype.     

A linkage group of five DNA markers on human chromosome 10

Five chromosome 10 DNA markers (D10S1, D10S3, D10S4, D10S5, and RBP3) were typed in five large pedigrees with multiple endocrine neoplasia type 2A (MEN-2A) and in five non-MEN-2A pedigrees. Linkage analyses showed that these loci and the locus for MEN-2A (MEN2A) are in one linkage group spanning at least 70 cM. The order of the marker loci is RBP3-D10S5-D10S3-D10S1-D10S4, with interlocus recombination frequencies of 7, 13-19, 19, and 19%, respectively, all on the same side of MEN2A. Analyses of sex-specific recombination frequencies indicated no significant differences between males and females for any of the map intervals studied. Previous localization of D10S5 and RBP3 to the proximal region of the long arm and the pericentric region, respectively, comparison of results with other studies, and our preliminary results with other chromosome 10 markers suggest that the D10S4 end of the map extends into the long arm. Our linkage map has been constructed using only two- and three-locus analyses. It will be possible to combine our results with those of other groups to construct a more detailed and accurate genetic map of chromosome 10.     

Beta beta homodimers exist in native rabbit skeletal muscle tropomyosin and increase after denaturation-renaturation.

Native tropomyosin from rabbit skeletal muscle (RSTm) consists mainly of alpha alpha and alpha beta coiled coils (alpha/beta approximately 3-4/1). In some extant studies, no beta beta molecules have been found. In this study, RSTm from several different preparations was disulfide cross-linked, both preparation and cross-linking being done under nondenaturing conditions. The cross-linked product was assayed for the presence of beta beta molecules cross-linked at both C36 and C190 (beta = beta). In such cross-linked RSTm, 3-8% beta = beta is detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis, C4 reversed-phase high-performance liquid chromatography, and a free-solution capillary electrophoresis experiment. This percentage becomes approximately 4-10% beta beta when corrected for incomplete double cross-linking and is independent of protein concentration (0.1-10.0 mg/mL), indicating that the observed beta beta species are not artifacts due to intermolecular cross-linking. Upon denaturation and subsequent renaturation either by heating to 55 degrees C or by incubating at 45 degrees C followed by quenching to room temperature, or by guanidine hydrochloride exposure followed by phased renaturation by dialysis, the fraction of beta beta increases, indicating that the reassociation favors homodimer formation somewhat over random association. This result differs from the random association observed when the sulfhydryl on one of the chains is carboxyamidomethylated (Holtzer, M.E., Breiner, T., & Holtzer, A., 1984, Biopolymers 23, 1811-1833), and from the overwhelming heterodimer preferences reported for tropomyosins from other organisms (Lehrer, S.S., Qian, Y., & Hvidt, S., 1989, Science 246, 926-928; Lehrer, S.S. & Qian, Y., 1990, J. Biol. Chem. 265, 1134-1138).     

Identification by molecular cloning of two forms of the alpha-subunit of the human liver stimulatory (GS) regulatory component of adenylyl cyclase

Two DNA molecules complementary to human liver mRNA coding for the alpha-subunit of the stimulatory regulatory component Gs of adenylyl cyclase were cloned. One of the two forms is a full-length cDNA of 1614 nucleotides plus a poly(A) tail of 59 nucleotides. The deduced sequence of 394 amino acids encoded by its open reading frame is essentially identical to that of the alpha-subunits of Gs identified by molecular cloning from bovine adrenals, bovine brain and rat brain. Two independent clones of the other type of cDNA were isolated. Both were incomplete, beginning within the open reading frame coding for the alpha s polypeptide. One codes for amino acids 5 through 394 and the other for amino acids 48 through 394 of the above described cDNA of 1614 nucleotides, and both have the identical 3'-untranslated sequence. They differ from the first cDNA, however, in that they lack a stretch of 42 nucleotides (numbers 214 through 255) and have nucleotides 213 (G) and 256 (G) replaced with C and A, respectively. This results in a predicted amino acid composition of another alpha-subunit of Gs that is shorter by 14 amino acids and contains two substitutions (Asp for Glu and Ser for Gly) at the interface between the deletion and the unchanged sequence. We call the smaller subunit alpha s1 and the larger alpha s2. This is the first demonstration of a structural heterogeneity in alpha s subunits that is due to a difference in amino acid sequence.     

Sequence homology between human alpha 1-antichymotrypsin, alpha 1-antitrypsin, and antithrombin III

alpha 1-Antichymotrypsin mRNA was isolated by specific polysome immunoprecipitation from turpentine-treated baboon liver. The highly enriched mRNA was used for synthesis and cloning of the corresponding cDNA. Baboon alpha 1-antichymotrypsin cDNA clones were identified by hybrid-selected translation, and the insert DNA fragment from one of the putative clones was used as a probe to screen a human liver cDNA library comprised of 40 000 independent transformants. One of the human cDNA clones was unambiguously identified to contain alpha 1-antichymotrypsin DNA sequences by comparison of its 5'-terminal nucleotide sequence with the N-terminal amino acid sequence of the protein. This cDNA clone, designated phACT235, contains 1524 base pairs of human DNA, which was sequenced in its entirety. The inserted DNA codes for a 25 amino acid signal peptide sequence and the entire mature alpha 1-antichymotrypsin of 408 amino acid residues. Comparison of the amino acid sequence of alpha 1-antichymotrypsin with that of the human alpha 1-antitrypsin has revealed a homology level similar to that between chymotrypsin and trypsin.     

Maternal morbidity associated with in utero transfer.

OBJECTIVE--To determine the extent of maternal morbidity associated with in utero transfer. DESIGN--Retrospective study of 190 consecutive cases over two years. SETTING--Liverpool Maternity Hospital. PATIENTS--190 Pregnant women were transferred to the hospital under the in utero transfer arrangements from district general hospitals both within and outside the Mersey region. The women admitted were divided into two categories: those in threatened or established uncomplicated preterm labour and those who may or may not have been in threatened or established preterm labour but who had coexisting complicating factors affecting the mother or fetus, or both. INTERVENTIONS--Planned delivery of the fetus if indicated and arrangements for appropriate postpartum care of the mother. MAIN OUTCOME MEASURE--Assessment of the progress of labour and, if appropriate, resuscitation of the mother. RESULTS--Women who were transferred with no coexisting disease (124) had relatively uncomplicated deliveries whereas those transferred with coexisting diseases (66) exhibited considerable morbidity and 17 of these required prolonged intensive monitoring after delivery. CONCLUSIONS--In utero transfer in healthy mothers may have benefits for babies born very prematurely. If mothers have coexisting disease, however, the desirability of transfer should be reviewed urgently in the light of the considerable maternal morbidity associated with these problems. In these cases transfer may introduce an additional hazard.