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  • 1
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 16, No. 3 ( 2006-03), p. 323-330
    Abstract: In the search for common genetic variants that contribute to prevalent human diseases, patterns of linkage disequilibrium (LD) among linked markers should be considered when selecting SNPs. Genotyping efficiency can be increased by choosing tagging SNPs (tagSNPs) in LD with other SNPs. However, it remains to be seen whether tagSNPs defined in one population efficiently capture LD in other populations; that is, how portable tagSNPs are. Indeed, tagSNP portability is a challenge for the applicability of HapMap results. We analyzed 144 SNPs in a 1-Mb region of chromosome 22 in 1055 individuals from 38 worldwide populations, classified into seven continental groups. We measured tagSNP portability by choosing three reference populations (to approximate the three HapMap populations), defining tagSNPs, and applying them to other populations independently on the availability of information on the tagSNPs in the compared population. We found that tagSNPs are highly informative in other populations within each continental group. Moreover, tagSNPs defined in Europeans are often efficient for Middle Eastern and Central/South Asian populations. TagSNPs defined in the three reference populations are also efficient for more distant and differentiated populations (Oceania, Americas), in which the impact of their special demographic history on the genetic structure does not interfere with successfully detecting the most common haplotype variation. This high degree of portability lends promise to the search for disease association in different populations, once tagSNPs are defined in a few reference populations like those analyzed in the HapMap initiative.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2006
    detail.hit.zdb_id: 1483456-X
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 21, No. 7 ( 2011-07), p. 1131-1138
    Abstract: One approach to understanding the genetic basis of traits is to study their pattern of inheritance among offspring of phenotypically different parents. Previously, such analysis has been limited by low mapping resolution, high labor costs, and large sample size requirements for detecting modest effects. Here, we present a novel approach to map trait loci using artificial selection. First, we generated populations of 10–100 million haploid and diploid segregants by crossing two budding yeast strains of different heat tolerance for up to 12 generations. We then subjected these large segregant pools to heat stress for up to 12 d, enriching for beneficial alleles. Finally, we sequenced total DNA from the pools before and during selection to measure the changes in parental allele frequency. We mapped 21 intervals with significant changes in genetic background in response to selection, which is several times more than found with traditional linkage methods. Nine of these regions contained two or fewer genes, yielding much higher resolution than previous genomic linkage studies. Multiple members of the RAS/cAMP signaling pathway were implicated, along with genes previously not annotated with heat stress response function. Surprisingly, at most selected loci, allele frequencies stopped changing before the end of the selection experiment, but alleles did not become fixed. Furthermore, we were able to detect the same set of trait loci in a population of diploid individuals with similar power and resolution, and observed primarily additive effects, similar to what is seen for complex trait genetics in other diploid organisms such as humans.
    Type of Medium: Online Resource
    ISSN: 1088-9051
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2011
    detail.hit.zdb_id: 1483456-X
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
    In: Genome Research, Cold Spring Harbor Laboratory, Vol. 11, No. 1 ( 2001-01-01), p. 170-178
    Abstract: The recent publication of the complete sequence of human chromosome 22 provides a platform from which to investigate genomic sequence variation. We report the identification and characterization of 12,267 potential variants (SNPs and other small insertions/deletions) of human chromosome 22, discovered in the overlaps of 460 clones used for the chromosome sequencing. We found, on average, 1 potential variant every 1.07 kb and approximately 18% of the potential variants involve insertions/deletions. The SNPs have been positioned both relative to each other, and to genes, predicted genes, repeat sequences, other genetic markers, and the 2730 SNPs previously identified on the chromosome. A subset of the SNPs were verified experimentally using either PCR–RFLP or genomic Invader assays. These experiments confirmed 92% of the potential variants in a panel of 92 individuals. [Details of the SNPs and RFLP assays can be found at http://www.sanger.ac.uk and in dbSNP.]
    Type of Medium: Online Resource
    ISSN: 1088-9051 , 1549-5469
    RVK:
    Language: English
    Publisher: Cold Spring Harbor Laboratory
    Publication Date: 2001
    detail.hit.zdb_id: 1483456-X
    SSG: 12
    Location Call Number Limitation Availability
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