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Marker Associations (marker + association)

Distribution by Scientific Domains

Life Sciences	100%

Selected Abstracts

Genome-wide scan for bovine twinning rate QTL using linkage disequilibrium

ANIMAL GENETICS, Issue 3 2009
E.-S. Kim
Summary Twinning is a complex trait with negative impacts on health and reproduction, which cause economic loss in dairy production. Several twinning rate quantitative trait loci (QTL) have been detected in previous studies, but confidence intervals for QTL location are broad and many QTL are unreplicated. To identify genomic regions or genes associated with twinning rate, QTL analysis based on linkage combined with linkage disequilibrium (LLD) and individual marker associations was conducted across the genome using high-throughput single nucleotide polymorphism (SNP) genotypes. A total of 9919 SNP markers were genotyped with 200 sires and sons in 19 half-sib North American Holstein dairy cattle families. After SNPs were genotyped, informative markers were selected for genome-wide association tests and QTL searches. Evidence for twinning rate QTL was found throughout the genome. Thirteen markers significantly associated with twinning rate were detected on chromosomes 2, 5 and 14 (P < 2.3 × 10,5). Twenty-six regions on fourteen chromosomes were identified by LLD analysis at P < 0.0007. Seven previously reported ovulation or twinning rate QTL were supported by results of single marker association or LLD analyses. Single marker association analysis and LLD mapping were complementary tools for the identification of putative QTL in this genome scan. [source]

Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chains

GENETIC EPIDEMIOLOGY, Issue 4 2008
Yunjung Kim
Abstract A map of the background levels of disequilibrium between nearby markers can be useful for association mapping studies. In order to assess the background levels of linkage disequilibrium (LD), multilocus LD measures are more advantageous than pairwise LD measures because the combined analysis of pairwise LD measures is not adequate to detect simultaneous allele associations among multiple markers. Various multilocus LD measures based on haplotypes have been proposed. However, most of these measures provide a single index of association among multiple markers and does not reveal the complex patterns and different levels of LD structure. In this paper, we employ non-homogeneous, multiple order Markov Chain models as a statistical framework to measure and partition the LD among multiple markers into components due to different orders of marker associations. Using a sliding window of multiple markers on phased haplotype data, we compute corresponding likelihoods for different Markov Chain (MC) orders in each window. The log-likelihood difference between the lowest MC order model (MC0) and the highest MC order model in each window is used as a measure of the total LD or the overall deviation from the gametic equilibrium for the window. Then, we partition the total LD into lower order disequilibria and estimate the effects from two-, three-, and higher order disequilibria. The relationship between different orders of LD and the log-likelihood difference involving two different orders of MC models are explored. By applying our method to the phased haplotype data in the ENCODE regions of the HapMap project, we are able to identify high/low multilocus LD regions. Our results reveal that the most LD in the HapMap data is attributed to the LD between adjacent pairs of markers across the whole region. LD between adjacent pairs of markers appears to be more significant in high multilocus LD regions than in low multilocus LD regions. We also find that as the multilocus total LD increases, the effects of high-order LD tends to get weaker due to the lack of observed multilocus haplotypes. The overall estimates of first, second, third, and fourth order LD across the ENCODE regions are 64, 23, 9, and 3%. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source]

Validation of whole genome linkage-linkage disequilibrium and association results, and identification of markers to predict genetic merit for twinning

ANIMAL GENETICS, Issue 4 2010
C. D. Bierman
Summary A previous genome-wide search with a moderate density 10K marker set identified many marker associations with twinning rate, either through single-marker analysis or combined linkage-linkage disequilibrium (LLD; haplotype) analysis. The objective of the current study was to validate putative marker associations using an independent set of phenotypic data. Holstein bulls (n = 921) from 100 paternal half-sib families were genotyped. Twinning rate predicted transmitting abilities were calculated using calving records from 1994 to 1998 (Data I) and 1999 to 2006 (Data II), and the underlying liability scores from threshold model analysis were used as the trait in marker association analyses. The previous analysis used 201 bulls with daughter records in Data I. In the current analysis, this was increased to 434, providing a revised estimate of effect and significance. Bulls with daughter records in Data II totaled 851, and analysis of this data provided the validation of results from analysis of Data I. Single nucleotide polymorphisms (SNPs) were selected to validate previously significant single-marker associations and LLD results. Bulls were genotyped for a total of 306 markers. Nine of 13 LLD regions located on chromosomes 1, 2, 3, 6, 9, 22, 23(2) and 26 were validated, showing significant results for both Data I and II. Association analysis revealed 55 of 174 markers validated, equating to a single-marker validation rate of 31%. Stepwise backward elimination and cross-validation analyses identified 18 SNPs for use in a final reduced marker panel explaining 34% of the genetic variation, and to allow prediction of genetic merit for twinning rate. [source]