Biomedical subjects

Jessica Roy

Publications and source records attributed to Jessica Roy.

4 recordsLinked to original sources

PubMed2005

Searching for signals of evolutionary selection in 168 genes related to immune function.

Pathogens have played a substantial role in human evolution, with past infections shaping genetic variation at loci influencing immune function. We selected 168 genes known to be involved in the immune response, genotyped common single nucleotide polymorphisms across each gene in three population samples (CEPH Europeans from Utah, Han Chinese from Guangxi, and Yoruba Nigerians from Southwest Nigeria) and searched for evidence of selection based on four tests for non-neutral evolution: minor allele frequency (MAF), derived allele frequency (DAF), Fst versus heterozygosity and extended haplotype homozygosity (EHH). Six of the 168 genes show some evidence for non-neutral evolution in this initial screen, with two showing similar signals in independent data from the International HapMap Project. These analyses identify two loci involved in immune function that are candidates for having been subject to evolutionary selection, and highlight a number of analytical challenges in searching for selection in genome-wide polymorphism data.

Algorithms↗

PubMed2005

The case for selection at CCR5-Delta32.

The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta32 arose within the past 1,000 y and rose to its present high frequency (5%-14%) in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5), they imply that the pattern of genetic variation seen at CCR5-Delta32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome.

Alleles↗

PubMed2002

The structure of haplotype blocks in the human genome.

Haplotype-based methods offer a powerful approach to disease gene mapping, based on the association between causal mutations and the ancestral haplotypes on which they arose. As part of The SNP Consortium Allele Frequency Projects, we characterized haplotype patterns across 51 autosomal regions (spanning 13 megabases of the human genome) in samples from Africa, Europe, and Asia. We show that the human genome can be parsed objectively into haplotype blocks: sizable regions over which there is little evidence for historical recombination and within which only a few common haplotypes are observed. The boundaries of blocks and specific haplotypes they contain are highly correlated across populations. We demonstrate that such haplotype frameworks provide substantial statistical power in association studies of common genetic variation across each region. Our results provide a foundation for the construction of a haplotype map of the human genome, facilitating comprehensive genetic association studies of human disease.

Africa↗

PubMedDate not supplied

Process utility in breast biopsy.

PURPOSE: To determine whether the waiting trade-off (WTO) is feasible for differentiating short-term biopsy preferences in an acute situation where anxiety is the symptomatic disease state. METHODS: 75 women with past experience of either breast core-needle biopsy (CNB), more invasive excisional surgical biopsy (EXB), or both, had telephone WTO assessments. Patients' baseline and test-related anxiety were valued by time trade-off (TTO) used to scale the WTO. Rating scales (RS) were obtained for convergent validity assessment with WTO and TTO. RESULTS: Data were obtained in 38 women who had both CNB and EXB ("paired") and 20 who had CNB only and 16 who had EXB only ("unpaired"). Patients rated only the procedure(s) they experienced. Median paired and mean unpaired WTO scores indicated patients were willing to wait significantly longer to avoid EXB (P = 0.0003, P = 0.0002, respectively). The waiting time difference between EXB and CNB was 2.1 weeks greater in unpaired data than paired data. RS scores comparing the procedures were significantly different only for paired data (P < 0.05). Median TTO preferences for baseline (1.00) and test anxiety (0.93) obtained in 74 patients were significantly different (P < 0.0001) and consistent with RS. Correlation was noted between WTO and RS (-0.307 to -0.453, P = 0.0205 to 0.0001). The median EXB quality-adjusted life years toll (1.5 quality-adjusted life days) calculated from pooled WTO data (paired and unpaired) from 54 patients is near a threshold in a published model. CONCLUSION: The WTO is feasible for discriminating preferences for short-term health states in an acute medical scenario where it might have been expected to be impracticable.

Adult↗