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      Genetic architecture of body size in mammals

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          Abstract

          Much of the heritability for human stature is caused by mutations of small-to-medium effect. This is because detrimental pleiotropy restricts large-effect mutations to very low frequencies.

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          Rare and common variants: twenty arguments.

          Greg Gibson (2011)
          Genome-wide association studies have greatly improved our understanding of the genetic basis of disease risk. The fact that they tend not to identify more than a fraction of the specific causal loci has led to divergence of opinion over whether most of the variance is hidden as numerous rare variants of large effect or as common variants of very small effect. Here I review 20 arguments for and against each of these models of the genetic basis of complex traits and conclude that both classes of effect can be readily reconciled.
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            Many sequence variants affecting diversity of adult human height.

            Daniel Gudbjartsson, G Walters, Gudmar Thorleifsson … (2008)
            Adult human height is one of the classical complex human traits. We searched for sequence variants that affect height by scanning the genomes of 25,174 Icelanders, 2,876 Dutch, 1,770 European Americans and 1,148 African Americans. We then combined these results with previously published results from the Diabetes Genetics Initiative on 3,024 Scandinavians and tested a selected subset of SNPs in 5,517 Danes. We identified 27 regions of the genome with one or more sequence variants showing significant association with height. The estimated effects per allele of these variants ranged between 0.3 and 0.6 cm and, taken together, they explain around 3.7% of the population variation in height. The genes neighboring the identified loci cluster in biological processes related to skeletal development and mitosis. Association to three previously reported loci are replicated in our analyses, and the strongest association was with SNPs in the ZBTB38 gene.
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              Genome-wide genetic association of complex traits in heterogeneous stock mice.

              William Valdar, Leah Solberg, Dominique Gauguier … (2006)
              Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits.
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                Author and article information

                Contributors
                Kathryn E Kemper
                Peter M Visscher
                Michael E Goddard
                Journal
                Journal ID (nlm-ta): Genome Biol
                Journal ID (iso-abbrev): Genome Biol
                Title: Genome Biology
                Publisher: BioMed Central
                ISSN (Print): 1465-6906
                ISSN (Electronic): 1465-6914
                Publication date (Print): 2012
                Publication date (Electronic): 30 April 2012
                Publication date PMC-release: 30 April 2013
                Volume: 13
                Issue: 4
                Page: 244
                Affiliations
                [1 ]Faculty of Land and Environment, University of Melbourne, Parkville, Victoria 3010, Australia
                [2 ]University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia
                [3 ]The Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia
                [4 ]Victorian Department of Primary Industries, AgriBiosciences Centre, LaTrobe Research and Development Park, Bundoora, Victoria 3083, Australia
                Article
                Publisher ID: gb-2012-13-4-244
                DOI: 10.1186/gb-2012-13-4-244
                PMC ID: 3446298
                PubMed ID: 22546202
                SO-VID: f38ef777-201f-4c18-9613-b41c9457d04b
                Copyright © Copyright ©2012 BioMed Central Ltd.
                History
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                Subject: Review

                ScienceOpen disciplines: Genetics
                Keywords: human height,mutation effects,mutation-selection balance
                Data availability:
                ScienceOpen disciplines: Genetics
                Keywords: human height, mutation effects, mutation-selection balance

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