It has been proposed that all live born females with Turner syndrome carry a cell line containing two sex chromosomes, which may be present at a low level of mosaicism (Hook & Warburton, 1983; Hassold et al. 1985; 1988; Connor & Loughlin, 1989). If the second sex chromosome is a Y, these patients are at risk of developing gonadoblastoma. In this study, 50 patients found to have a 45,X karyotype by conventional cytogenetic analysis, were screened by the polymerase chain reaction (PCR), for the presence of Y chromosome sequences. Two patients were positive for six of the eight Y chromosome loci tested and additional cytogenetic analysis confirmed the presence of a marker chromosome, in 8% and 3% of cells respectively. Fluorescence in situ hybridization (FISH) was used to confirm that the markers were of Y chromosome origin and helped to elucidate their structure. In addition, four other patients were found to have a Y chromosome by initial routine cytogenetic analysis. FISH, in conjunction with PCR, elucidated the structure of the Y chromosomes. This study illustrates the value of using a combination of cytogenetic and molecular techniques, to identify Y chromosome sequences in Turner syndrome.

Rhnull is a syndrome serologically characterized by the deficiency of all Rh antigens on human red blood cells. Rhnull is divided into two types: regulator and amorph. Recently, Cherif-Zahar et al. proposed that the RHAG gene encoding the Rh50 glycoprotein is a candidate for inducing regulator type Rhnull. We investigated both the RH and RHAG genes in an Rhnull individual. The reticulocytes from the propositus had RHD, RHcE, and RHCe transcripts without any mutation. However, the sequence analysis of RHAG cDNA showed a deletion of 122 bp from nucleotide 946 to 1067. This deletion was revealed to be due to a homozygous splicing mutation, which is a single base substitution at the consensus sequence of the splicing acceptor site (AG→AT). The mutation appeared to break the ‘GT-AG’ splicing rule and to cause 122 bp exon skipping accompanied by a frameshift. This study confirms that the RHAG gene is the most likely candidate for the ‘regulator’ gene of Rhnull cases.

The analysis of seven different age cohorts (697 individuals from 10 to 109 years old) revealed age-related changes in the 3′APOB-VNTR genotype pool. By recoding the 3′APOB-VNTR alleles into three size-classes (small, S, 26–34 repeats; medium, M, 35–39 repeats; large, L, 41–55 repeats), an age-related convex trajectory of the frequency of SS homozygotes was found. The frequency of SS in the genotype pool increased from the group aged 10–19 years (3.06±1.74%) to that aged 40–49 years (8.51±4.07%). Then it declined reaching the minimum value in centenarians (1.58±0.90%). The observed trajectory is in agreement with that expected by assuming crossing of mortality curves relevant to subgroups of individuals having different genotypes.

To examine the possible internal heterogeneity within the Basque population, nine samples typed for several HLA loci were compiled and HLA-A, B, C and DR loci were analysed. First, the shared features of HLA in Basques were analysed by principal component analysis and genetic distances. Two major Basque dialect groups (‘French’ and ‘Spanish’) were considered. FST statistics were computed and corrected for sampling intensity. The dialectal and political division did not seem to differentiate these two groups genetically. Analysis of Molecular Variance also failed to show consistently significant genetic variance components between French and Spanish Basques. Thus, in this particular example, linguistic diversity does not seem to correlate with a genetic stratification.

Two sets of markers and populations were considered in this study: (a) the variability at 17 protein loci and in the sequences of the first hypervariable segment of the mitochondrial DNA (mtDNA) were compared in 10 South American Indian tribes, in a total 3016 and 241 individuals, respectively; and (b) a triple comparison was made, in relation to 17 protein, mtDNA and six hypervariable tandem repeat loci in four Brazilian Indian tribes, involving 1567, 56 and 194 persons, respectively. Both the intrapopulational diversities and the population relationships obtained in these groups with these different sets of markers showed no significant correlation. High levels of heterogeneity were observed both at the protein and hypervariable individual loci, as well between mtDNA sites. The different positions observed for the Yanomama (but not for the other nine tribes) in the trees which summarized the protein and mtDNA data suggest some degree of asymmetric interchange related to sex between them and neighbouring tribes.

The effect of consanguinity and inbreeding on spontaneous abortion is assessed with the help of data from a population-based study conducted in four squatter settlements of Karachi, Pakistan. The analysis is based on 4966 pregnancy records belonging to 873 women. Results of the multivariate analysis show that both consanguinity and inbreeding were independent risk factors for spontaneous abortion despite undertaking control for other biological and socio-demographic factors that could confound the association. The combination of fetal and parental inbreeding led to a greater likelihood of a pregnancy ending in spontaneous abortion than one generation of inbreeding alone.

I compare the transmission/disequilibrium test (TDT) and affected sib pair (ASP) test under a general algebraic model describing a bi-allelic disease locus. Assuming linkage to a bi-allelic marker, I derive two binomial probabilities, one for parental allele ‘transmission’ (Pt ) which determines the magnitude of the TDT χ2 statistic (χ2tdt), and a second for identity-by-descent (ibd) marker allele ‘sharing’ (Ps) which determines the magnitude of the ASP test statistic (χ2asp). I also consider the ASP test applied to a completely polymorphic marker and demonstrate that the probability of ASP marker allele sharing (Ps) is identical to Ps observed for a bi-allelic marker in equilibrium with the disease locus. I present a general framework for determining the power of the TDT and ASP test based on expressions for Pt, Ps and the proportion (H/F) of ascertained parents who are informative at the marker. Two previous analytic investigations of TDT power based on the work of Ott (1989), and Risch & Merikangas (1996) are shown to be special cases of this general framework. In addition, I show the relationship between the framework I present and a third analytic investigation of TDT power for multi-allelic markers based on the work of Sham & Curtis (1995).

Four sequence variants in the 11β-hydroxylase (CYP11B1) gene are reported. One of the sequence changes occurs in exon 1 and is in linkage disequilibrium with a second variant in intron 3. The other two changes occur at adjacent nucleotides in intron 1. The finding of easily demonstrable, intragenic variants will be beneficial to the study of the role of the CYP11B1 and the adjacent aldosterone synthase (CYP11B2) gene in hypertensive disease.