Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Response of a Lake Michigan coastal lake to anthropogenic catchment disturbance

A paleolimnological investigation of post-European sediments in a Lake Michigan coastal lake was used to examine the response of Lower Herring Lake to anthropogenic impacts and its role as a processor of watershed inputs. We also compare the timing of this response with that of Lake Michigan to examine the role of marginal lakes as ‘early warning’ indicators of potential changes in the larger connected system and their role in buffering Lake Michigan against anthropogenic changes through biotic interactions and material trapping. Sediment geochemistry, siliceous microfossils and nutrient-related morphological changes in diatoms, identified three major trophic periods in the recent history of the lake. During deforestation and early settlement (pre-1845–1920), lake response to catchment disturbances results in localized increases in diatom abundances with minor changes in existing communities. In this early phase of disturbance, Lower Herring Lake acts as a sediment sink and a biological processor of nutrient inputs. During low-lake levels of the 1930s, the lake goes through a transitional period characterized by increased primary productivity and a major shift in diatom communities. Post-World War II (late 1940s–1989) anthropogenic disturbances push Lower Herring Lake to a new state and a permanent change in diatom community structure dominated by Cyclotella comensis . The dominance of planktonic summer diatom species associated with the deep chlorophyll maximum (DCM) is attributed to epilimnetic nutrient depletion. Declining Si:P ratios are inferred from increased sediment storage of biogenic silica and morphological changes in the silica content of Aulacoseira ambigua and Stephanodiscus niagarae . Beginning in the late 1940s, Lower Herring Lake functions as a biogeochemical processor of catchment inputs and a carbon, nutrient and silica sink. Microfossil response to increased nutrients and increased storage of biogenic silica in Lower Herring Lake and other regional embayments occur approximately 20–25 years earlier than in a nearby Lake Michigan site. Results from this study provide evidence for the role of marginal lakes and bays as nutrient buffering systems, delaying the impact of anthropogenic activities on the larger Lake Michigan system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43091/1/10933_2004_Article_1688.pd