Allele Spectrum of Human Genetic Disease

Kenneth M Weiss, Pennsylvania State University, University Park, Pennsylvania, USA

Published online: January 2006

DOI: 10.1038/npg.els.0006033

The distribution of genetic variation associated with a specified phenotype is sometimes known as its genetic architecture or allele frequency ‘spectrum’. These terms may refer to a disease phenotype or to variation in the trait in the general population.

Keywords: genetic architecture; allele frequencies; allele spectrum; genotype–phenotype relationships; genetic variation

Figure 1. Frequency spectrum of the rarer allele at 5211 polymorphic sites in 70 genes, in random samples of 48 African-American and 46 European chromosomes. Alleles present in both populations, gray bars; only in one population, hatched bars. SNP: single nucleotide polymorphism. Courtesy Nickerson D (http://pga.mbt.washington.edu/genes_p1.html).
Figure 2. Relative frequencies of 444 alleles associated with PKU (source PAHdb).
Figure 3. Location of mutations at the genes responsible for (a) PKU: I, E, U introns, exons and untranslated regions respectively; and (b) cystic fibrosis: different types of mutation in each row, location relative to exons (top scale) and functional areas in protein (lower scale). Bar thickness proportional to observed frequency (sources: (a) PAHdb; (b) CFdb database).
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 References
    Beutler E, Felitti VJ, Koziol JA, Ho NJ and Gelbart T (2002) Penetrance of 845GA (C282Y) HFE hereditary haemochromatosis mutation in the USA. The Lancet 359: 211–218.
    Goring HH, Terwilliger JD and Blangero J (2001) Large upward bias in estimation of locus-specific effects from genomewide scans. American Journal of Human Genetics 69: 1357–1369.
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 Web Links
    ePath CFDB (cystic fibrosis mutation data base) http://www.genet.sickkids.on.ca/cftr/
    ePath HMGD (human gene mutation data base) http://archive.uwcm.ac.uk/uwcm/mg/hgmd0.html
    ePath OMIM (online Mendelian inheritance in man) http://www.ncbi.nlm.nih.gov
    ePath PAHdb (phenylalanine hydroxylase data base) http://data.mch.mcgill.ca/pahdb_new/

Related Sub-Topics:

Evolutionary Processes | Population Structure and Genetics | Evolution Rates | Statistical Methodology in Genetics | Inter-Individual Variation and Polymorphism | General Genetics and Disease
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Article Title: Allele Spectrum of Human Genetic Disease
 
How to Cite close
Weiss, Kenneth M(Jan 2006) Allele Spectrum of Human Genetic Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006033]