Biomedical subjects

Badri Padhukasahasram

Publications and source records attributed to Badri Padhukasahasram.

5 recordsLinked to original sources

PubMed2006

Estimating recombination rates from single-nucleotide polymorphisms using summary statistics.

We describe a novel method for jointly estimating crossing-over and gene-conversion rates from population genetic data using summary statistics. The performance of our method was tested on simulated data sets and compared with the composite-likelihood method of R. R. Hudson. For several realistic parameter values, the new method performed similarly to the composite-likelihood approach for estimating crossing-over rates and better when estimating gene-conversion rates. We used our method to analyze a human data set recently genotyped by Perlegen Sciences.

Computer Simulation↗

PubMed2005

Relative influences of crossing over and gene conversion on the pattern of linkage disequilibrium in Arabidopsis thaliana.

In this article we infer the rates of gene conversion and crossing over in Arabidopsis thaliana from population genetic data. Our data set is a genomewide survey consisting of 1347 fragments of length 600 bp sequenced in 96 accessions. It has several orders of magnitude more markers than any previous nonhuman study. This allows for more accurate inference as well as a detailed comparison between theoretical expectations and observations. Our methodology is specifically set to account for deviations such as recurrent mutations or a skewed frequency spectrum. We found that even if some components of the model clearly do not fit, the pattern of LD conforms to theoretical expectations quite well. The ratio of gene conversion to crossing over is estimated to be around one. We also find evidence for fine-scale variations of the crossing-over rate.

Arabidopsis↗

PubMed2005

The pattern of polymorphism in Arabidopsis thaliana.

We resequenced 876 short fragments in a sample of 96 individuals of Arabidopsis thaliana that included stock center accessions as well as a hierarchical sample from natural populations. Although A. thaliana is a selfing weed, the pattern of polymorphism in general agrees with what is expected for a widely distributed, sexually reproducing species. Linkage disequilibrium decays rapidly, within 50 kb. Variation is shared worldwide, although population structure and isolation by distance are evident. The data fail to fit standard neutral models in several ways. There is a genome-wide excess of rare alleles, at least partially due to selection. There is too much variation between genomic regions in the level of polymorphism. The local level of polymorphism is negatively correlated with gene density and positively correlated with segmental duplications. Because the data do not fit theoretical null distributions, attempts to infer natural selection from polymorphism data will require genome-wide surveys of polymorphism in order to identify anomalous regions. Despite this, our data support the utility of A. thaliana as a model for evolutionary functional genomics.

Arabidopsis↗

PubMed2004

Estimating the rate of gene conversion on human chromosome 21.

There is a growing recognition that gene conversion can be an important factor in shaping fine-scale patterns of linkage disequilibrium in the human genome. We devised simple multilocus summary statistics for estimating gene-conversion rates from genomewide polymorphism data sets. In addition to being computationally feasible for very large data sets, these summaries were designed to yield robust estimates of gene-conversion rates in the presence of variation in crossing-over rates. Using our summaries, we analyzed 21,840 biallelic single-nucleotide polymorphisms (SNPs) on human chromosome 21. Our results indicate that models including both crossing over and gene conversion fit the overall short-range data (0-5 kb) of chromosome 21 much better than do models including crossing over alone. The estimated ratio of gene-conversion rate to crossing-over rate has a range of 1.6-9.4, depending on the assumed conversion tract length (in the range of 500-50 bp). Removal of the 5,696 SNPs that occur in known mutational hotspots (CpG sites) did not significantly change our conclusions, suggesting that recurrent mutations alone cannot explain our data.

Chromosome Aberrations↗

PubMed2003

The pattern of polymorphism on human chromosome 21.

Polymorphism data from 20 partially resequenced copies of human chromosome 21-more than 20,000 polymorphic sites-were analyzed. The allele-frequency distribution shows no deviation from the simplest population genetic model with a constant population size (although we show that our analysis has no power to detect population growth). The average rate of recombination per site is estimated to be roughly one-half of the rate of mutation per site, again in agreement with simple model predictions. However, sliding-window analyses of the amount of polymorphism and the extent of linkage disequilibrium (LD) show significant deviations from standard models. This could be due to the history of selection or demographic change, but it is impossible to draw strong conclusions without much better knowledge of variation in the relationship between genetic and physical distance along the chromosome.

Alleles↗