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Variants of different Class I alcohol dehydrogenase (ADH) genes have been shown to be associated with an effect that is protective against alcoholism. Previous work from our laboratory has shown that the two sites showing the association are in linkage disequilibrium and has identified the ADH1B Arg47His site as causative, with the ADH1C Ile349Val site showing association only because of the disequilibrium. Here, we describe an initial study of the nature of linkage disequilibrium and genetic variation, in population samples from different regions of the world, in a larger segment of the ADH cluster (including the three Class I ADH genes and ADH7). Linkage disequilibrium across approximately 40 kb of the Class I ADH cluster is moderate to strong in all population samples that we studied. We observed nominally significant pairwise linkage disequilibrium, in some populations, between the ADH7 site and some Class I ADH sites, at moderate values and at a molecular distance as great as 100 kb. Our data indicate (1) that most ADH-alcoholism association studies have failed to consider many sites in the ADH cluster that may harbor etiologically significant alleles and (2) that the relevance of the various ADH sites will be population dependent. Some individual sites in the Class I ADH cluster show Fst values that are among the highest seen among several dozen unlinked sites that were studied in the same subset of populations. The high Fst values can be attributed to the discrepant frequencies of specific alleles in eastern Asia relative to those in other regions of the world. These alleles are part of a single haplotype that exists at high (>65%) frequency only in the eastern-Asian samples. It seems unlikely that this haplotype, which is rare or unobserved in other populations, reached such high frequency because of random genetic drift alone.

Context: Nigerian adolescents generally have low levels of contraceptive use, but their reliance on unsafe abortion is high, and results in many abortion-related complications. To determine why, it is important to investigate adolescents' perceptions concerning the risks of contraceptive use versus those of induced abortion. Methods: Data were collected through focus-group discussions held with adolescents of diverse educational and socioeconomic backgrounds. All were asked what they knew about abortion and contraception, and each method of contraception was discussed in detail. In particular, youths were asked about contraceptive availability, perceived advantages of method use, side effects and young people's reasons for using or not using contraceptives. Results: Fear of future infertility was an overriding factor in adolescents' decisions to rely on induced abortion rather than contraception. Many focus-group participants perceived the adverse effects of modern contraceptives on fertility to be continuous and prolonged, while they saw abortion as an immediate solution to an unplanned pregnancy-and, therefore, one that would have a limited negative impact on future fertility. This appears to be the major reason why adolescents prefer to seek induced abortion rather than practice effective contraception. Conclusions: The need to educate adolescents about the mechanism of action of contraceptive agents and about their side effects in relation to unsafe abortion is paramount if contraceptive use is to be improved among Nigerian adolescents.

No abstract

SummaryThe catalytic deficiency of human aldehyde dehydrogenase 2 (ALDH2) is caused by a nucleotide substitution (G1510A; Glu487Lys) in exon 12 of the ALDH2 locus. This SNP, and four non-coding SNPs, including one in the promoter, span 40 kb of ALDH2; these and one downstream STRP have been tested in 37 worldwide populations. Only four major SNP-defined haplotypes account for almost all chromosomes in all populations. A fifth haplotype harbours the functional variant and is only found in East Asians. Though the SNPs showed virtually no historic recombination, LD values are quite variable because of varying haplotype frequencies, demonstrating that LD is a statistical abstraction and not a fundamental aspect of the genome, and is not a function solely of recombination. Among populations, different sets of tagging SNPs, sometimes not overlapping, can be required to identify the common haplotypes. Thus, solely because haplotype frequencies vary, there is no common minimum set of tagging SNPs globally applicable. The F st values of the promoter region SNP and the functional SNP were about two S.D. above the mean for a reference distribution of 117 autosomal biallelic markers. These high F st values may indicate selection has operated at these or very tightly linked sites.