Evaluating Human Genetic Diversity (1997) / Chapter Skim
Currently Skimming:
3 SAMPLING ISSUES
3 SAMPLING ISSUES
Pages 23-35
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 23... ...
Regardless of sampling strategy, the introduction of any sample into a repository raises the following questions: · In addition to the samples themselves, what information should be collected from each person in the survey? · What types of samples should be collected (for example, blood, buccal cells, and hair roots)
|
From page 24... ...
Nevertheless, it is impractical to devise a single sampling scheme that would be amenable to testing all possible hypotheses. For example, many sampling designs in medical genetics require case-control sampling (in which a subset of the total sample contains subjects who have a specific disease state and the rest of the subjects are matched to the diseased persons with respect to sex, age, or other variables)
|
From page 25... ...
In particular, it could be used to test hypotheses about human genome evolution, patterns of genetic variation relative to functional types of DNA and location in the genome, and the total amount of genetic variation found in the human species. The other classes of hypotheses given in chapter 2 would not be amenable to testing with a sample that does not identify individuals, or geographic areas or populations, so this sampling scheme is associated with a narrow breadth of applicability.
|
From page 26... ...
26 Cal a' .= a' so big VO ¢ EM V, ca m o to V, ca m o to 1 o Z ca in + ~ 4= ·0 C.)
|
From page 27... ...
The recent studies on human genetic variation have generated controversy, largely because the available samples from human populations are geographically inadequate to test them (Templeton 1993~. Thus, there remains a great need for the type of population-level samples that would result from coordinated global sampling of human genetic variation.
|
From page 28... ...
or that they have exchanged genes repeatedly throughout all recent human evolutionary history, so there is only a single evolutionary lineage of humanity (Templeton 1994, 1996~. Further sampling will help to determine which of those two alternatives is correct.
|
From page 29... ...
When pedigree data are gathered with population and phenotypic data, more-definitive phenotypic studies are possible and they have enhanced power to detect markers close enough to disease loci to produce a within-family association even in the absence of a populationlevel association, as in the case of Huntington chorea in the Lake Maracaibo area of Venezuela (Gusella and others 1983~. Moreover, when many closely linked marker loci exhibit heterozygosity, family data often allow the construction of haplotypes with more certainty.
|
From page 30... ...
There have been sufficient studies to show that overall levels and patterns of human genomic diversity show little between-population variation in a quantitative sense (Barbujani and others 1997) , so the hypotheses to be tested under sampling strategy I do not require sampling of any new or additional populations.
|
From page 31... ...
Sampling strategy III offers the best balance of breadth of testable hypotheses, expense, and ethical complications. Recommendation 3.1: A coordinated global sampling effort to develop a common resource for research on human genome variation should use a population-based sampling design in which the geographic location of the sample and self-reported ethnicity, primary language, sex, age, and parental
|
From page 32... ...
For example, hypotheses about the effect of technologic changes on population structure and gene flow patterns might be of interest, or HLA frequencies in recently admixed populations or genetic-disease associations with systemic diseases that affect primarily populations in developed countries. Underrepresenting such populations would yield a biased sample for studying overall human evolution and restrict the overall biomedical utility of the sample.
|
From page 33... ...
For example, although studies on human mitochondrial DNA have attracted much attention as a tool for exploring recent human evolution, testing with rigorous statistical criteria even fundamental hypotheses regarding whether mitochondrial variation spread around the globe through recurrent gene flow or population replacement is not possible, because few populations have been sampled in a geographically accurate manner (Templeton 1993~. The only mitochondrial-DNA data set that even barely satisfied the sampling requirements of recent statistical tests designed to discriminate between gene flow and population replacement is that assembled by Excoffier (1990)
|
From page 34... ...
Because human populations show so little overall genetic differentiation, large samples will be needed to perform such studies. For example, the e4 allele at the Apo-E locus on chromosome 19 has been shown to have a large and significant effect on the chance of death from coronary arterial disease, the largest cause of death in the developed countries (Stengard and others 1995~.
|
From page 35... ...
Strategy I does not provide a rationale for global sampling, and strategy II has many of the same ethical complications as strategy III but with a substantial restriction in breadth of testable hypotheses. Strategies IV and V could greatly increase the cost, complicate sampling logistics, raise serious ethical and security concerns, and benefit only a few investigators (although the investigations that would be so benefited have the most-direct biomedical relevance)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.