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Gabor T Marth

Publications and source records attributed to Gabor T Marth.

3 recordsLinked to original sources
PubMed2005

Analysis of concordance of different haplotype block partitioning algorithms.

BACKGROUND: Different classes of haplotype block algorithms exist and the ideal dataset to assess their performance would be to comprehensively re-sequence a large genomic region in a large population. Such data sets are expensive to collect. Alternatively, we performed coalescent simulations to generate haplotypes with a high marker density and compared block partitioning results from diversity based, LD based, and information theoretic algorithms under different values of SNP density and allele frequency. RESULTS: We simulated 1000 haplotypes using the standard coalescent for three world populations--European, African American, and East Asian--and applied three classes of block partitioning algorithms--diversity based, LD based, and information theoretic. We assessed algorithm differences in number, size, and coverage of blocks inferred under different conditions of SNP density, allele frequency, and sample size. Each algorithm inferred blocks differing in number, size, and coverage under different density and allele frequency conditions. Different partitions had few if any matching block boundaries. However they still overlapped and a high percentage of total chromosomal region was common to all methods. This percentage was generally higher with a higher density of SNPs and when rarer markers were included. CONCLUSION: A gold standard definition of a haplotype block is difficult to achieve, but collecting haplotypes covered with a high density of SNPs, partitioning them with a variety of block algorithms, and identifying regions common to all methods may be the best way to identify genomic regions that harbor SNP variants that cause disease.

Algorithms↗
PubMed2004

The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations.

We have studied a genome-wide set of single-nucleotide polymorphism (SNP) allele frequency measures for African-American, East Asian, and European-American samples. For this analysis we derived a simple, closed mathematical formulation for the spectrum of expected allele frequencies when the sampled populations have experienced nonstationary demographic histories. The direct calculation generates the spectrum orders of magnitude faster than coalescent simulations do and allows us to generate spectra for a large number of alternative histories on a multidimensional parameter grid. Model-fitting experiments using this grid reveal significant population-specific differences among the demographic histories that best describe the observed allele frequency spectra. European and Asian spectra show a bottleneck-shaped history: a reduction of effective population size in the past followed by a recent phase of size recovery. In contrast, the African-American spectrum shows a history of moderate but uninterrupted population expansion. These differences are expected to have profound consequences for the design of medical association studies. The analytical methods developed for this study, i.e., a closed mathematical formulation for the allele frequency spectrum, correcting the ascertainment bias introduced by shallow SNP sampling, and dealing with variable sample sizes provide a general framework for the analysis of public variation data.

Black or African American↗