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A genome-wide survey of human short-term memory.

ABSTRACT: Recent advances in the development of high-throughput genotyping platforms allow for the unbiased identification of genes and genomic sequences related to heritable traits. In this study, we analyzed human short-term memory, which refers to the ability to remember information over a brief period of time and which has been found disturbed in many neuropsychiatric conditions, including schizophrenia and depression. We performed a genome-wide survey at 909?622 polymorphic loci and report six genetic variations significantly associated with human short-term memory performance after genome-wide correction for multiple comparisons. A polymorphism within SCN1A (encoding the ? subunit of the type I voltage-gated sodium channel) was replicated in three independent populations of 1699 individuals. Functional magnetic resonance imaging during an n-back working memory task detected SCN1A allele-dependent activation differences in brain regions typically involved in working memory processes. These results suggest an important role for SCN1A in human short-term memory.

SUBMITTER: Papassotiropoulos A

PROVIDER: S-EPMC3030750 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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A genome-wide survey of human short-term memory.

Papassotiropoulos A A Henke K K Stefanova E E Aerni A A Müller A A Demougin P P Vogler C C Sigmund J C JC Gschwind L L Huynh K-D KD Coluccia D D Mondadori C R CR Hänggi J J Buchmann A A Kostic V V Novakovic I I van den Bussche H H Kaduszkiewicz H H Weyerer S S Bickel H H Riedel-Heller S S Pentzek M M Wiese B B Dichgans M M Wagner M M Jessen F F Maier W W de Quervain D J-F DJ

Molecular psychiatry 20091229 2

Recent advances in the development of high-throughput genotyping platforms allow for the unbiased identification of genes and genomic sequences related to heritable traits. In this study, we analyzed human short-term memory, which refers to the ability to remember information over a brief period of time and which has been found disturbed in many neuropsychiatric conditions, including schizophrenia and depression. We performed a genome-wide survey at 909 622 polymorphic loci and report six geneti ...[more]

PMID: 20038948

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Project description:Despite evolutionary biology's obsession with natural selection, few studies have evaluated multi-generational series of patterns of selection on a genome-wide scale in natural populations. Here, we report on a nine-year population-genomic survey of the microcrustacean Daphnia pulex. The genome-sequences of > 800 isolates provide insights into patterns of selection that cannot be obtained from long-term molecular-evolution studies, including the pervasiveness of near quasi-neutrality across the genome (mean net selection coefficients near zero, but with significant temporal variance about the mean, and little evidence of positive covariance of selection across time intervals), the preponderance of weak negative selection operating on minor alleles, and a genome-wide distribution of numerous small linkage islands of observable selection influencing levels of nucleotide diversity. These results suggest that fluctuating selection is a major determinant of standing levels of variation in natural populations, challenge the conventional paradigm for interpreting patterns of nucleotide diversity and divergence, and motivate the need for the development of new theoretical expressions for the interpretation of population-genomic data.SignificanceExcept for mono/oligogenic traits known in advance to be under strong selection, there is little information on genome-wide patterns of temporal dynamics of allele-frequency changes in well-defined and unmanipulated natural populations. A multi-year survey of a population of the microcrustacean Daphnia pulex provides insight into these matters. Genome-wide analysis of > 800 genetic isolates demonstrates that temporal variation in selection intensity is a major determinant of levels of nucleotide polymorphism and divergence. Most nucleotide sites experience fluctuating selection with mean selection coefficients near zero, with little covariance in the strength of selection across time intervals, and with selection distributed across large numbers of genomic islands of linked sites. These results raise challenges for the conventional interpretation of measures of nucleotide diversity and divergence as indicators of effective population sizes and intensities of positive/negative selection.

Dataset Information

A genome-wide survey of human short-term memory.

Publications

A genome-wide survey of human short-term memory.

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