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Shades of gray: a comparison of linkage disequilibrium between Hutterites and Europeans.

ABSTRACT: Founder or isolated populations have advantages for genetic studies due to decreased genetic and environmental heterogeneity. However, whereas longer-range linkage disequilibrium (LD) in these populations is expected to facilitate gene localization, extensive LD may actually limit the ability for gene discovery. The North American Hutterite population is one of the best characterized young founder populations and members of this isolate have been the subjects of our studies of complex traits, including fertility, asthma and cardiovascular disease, for >20 years. Here, we directly assess the patterns and extent of global LD using single nucleotide polymorphism genotypes with minor allele frequencies (MAFs) > or =5% from the Affymetrix GeneChip Mapping 500 K array in 60 relatively unrelated Hutterites and 60 unrelated Europeans (HapMap CEU). Although LD among some marker pairs extends further in the Hutterites than in Europeans, the pattern of LD and MAF are surprisingly similar. These results indicate that (1) identifying disease genes should be no more difficult in the Hutterites than in outbred European populations, (2) the same common susceptibility alleles for complex diseases should be present in the Hutterites and outbred European populations, and (3) imputation algorithms based on HapMap CEU should be applicable to the Hutterites.

SUBMITTER: Thompson EE

PROVIDER: S-EPMC4238926 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Shades of gray: a comparison of linkage disequilibrium between Hutterites and Europeans.

Thompson Emma E EE Sun Ying Y Nicolae Dan D Ober Carole C

Genetic epidemiology 20100201 2

Founder or isolated populations have advantages for genetic studies due to decreased genetic and environmental heterogeneity. However, whereas longer-range linkage disequilibrium (LD) in these populations is expected to facilitate gene localization, extensive LD may actually limit the ability for gene discovery. The North American Hutterite population is one of the best characterized young founder populations and members of this isolate have been the subjects of our studies of complex traits, in ...[more]

PMID: 19697328

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Project description:BackgroundThe success of genome-wide scans depends on the strength and magnitude of linkage disequilibrium (LD) present within the populations under investigation. High density SNP arrays are currently in development for the sheep genome, however little is known about the behaviour of LD in this livestock species. This study examined the behaviour of LD within five sheep populations using two LD metrics, D' and x2'. Four economically important Australian sheep flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a crossbred population (Merino x Border Leicester), along with an inbred Australian Merino museum flock were analysed.ResultsShort range LD (0 - 5 cM) was observed in all five populations, however the persistence with increasing distance and magnitude of LD varied considerably between populations. Average LD (x2') for markers spaced up to 20 cM exceeded the non-syntenic average within the White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within the Merino and Merino x Border Leicester, with LD below or consistent with observed background levels. Using marker-marker LD as a guide to the behaviour of marker-QTL LD, estimates of minimum marker spacing were made. For a 95% probability of detecting QTL, a microsatellite marker would be required every 0.1 - 2.5 centimorgans, depending on the population used.ConclusionSheep populations were selected which were inbred (Macarthur Merino), highly heterogeneous (Merino) or intermediate between these two extremes. This facilitated analysis and comparison of LD (x2') between populations. The strength and magnitude of LD was found to differ markedly between breeds and aligned closely with both observed levels of genetic diversity and expectations based on breed history. This confirmed that breed specific information is likely to be important for genome wide selection and during the design of successful genome scans where tens of thousands of markers will be required.

Dataset Information

Shades of gray: a comparison of linkage disequilibrium between Hutterites and Europeans.

Publications

Shades of gray: a comparison of linkage disequilibrium between Hutterites and Europeans.

Similar Datasets

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