Tuesday, January 7, 2014

In print: Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar

Just published in Human Mutationour second article on disease risk allele prevalence in Qatar.

This study presents a framework for enabling precision genome-based medicine (PGM) in a population not sampled by nor related to public consortium sequencing projects, using the example of Qatar. Through sampling and exome sequencing of representatives from three major ancestry groups identified in prior work (Q1 Bedouin, Q2 Persian-South Asian, Q3 African), we identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. Genetic screening in Qatar includes only 4 out of the 37. This study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance.

Wednesday, March 20, 2013

My first paper as lead author at Cornell: Exome Sequencing of Only Seven Qataris Identifies Potentially Deleterious Variants in the Qatari Population

The Qatari population, located at the Arabian migration crossroads of African and Eurasia, is comprised of Bedouin, Persian and African genetic subgroups. By deep exome sequencing of only 7 Qataris, including individuals in each subgroup, we identified 2,750 nonsynonymous SNPs predicted to be deleterious, many of which are linked to human health, or are in genes linked to human health. Many of these SNPs were at significantly elevated deleterious allele frequency in Qataris compared to other populations worldwide. Despite the small sample size, SNP allele frequency was highly correlated with a larger Qatari sample. Together, the data demonstrate that exome sequencing of only a small number of individuals can reveal genetic variations with potential health consequences in understudied populations. Full Text

Wednesday, March 7, 2012

Word cloud of my dissertation

It's been a while since I posted here. Was testing out Twitter, but not having fun and miss blogging. My dissertation is available online now. Here is a word cloud summary.

Tuesday, May 18, 2010

In populo as a new scientific term!


Friday, March 26, 2010

Abstract of my first article, published in Mammalian Genome.

Conserved regulatory motifs at phenylethanolamine N-methyltransferase (PNMT) are disrupted by common functional genetic variation: an integrated computational/experimental approach
Mammalian Genome: Volume 21, Issue 3 (2010), Page 195.

Juan L. Rodríguez-Flores1, 2, 4 Contact Information, Kuixing Zhang1, Sun Woo Kang1, 3, Gen Wen1, Sajalendu Ghosh1, Ryan S. Friese1, Sushil K. Mahata1, Shankar Subramaniam2, Bruce A. Hamilton1 and Daniel T. O’Connor1
(1) Department of Medicine, Institute for Genomic Medicine, University of California at San Diego School of Medicine, La Jolla, CA, USA
(2) Department of Bioengineering, University of California at San Diego, La Jolla, CA, USA
(3) Department of Nephrology, Inje University, Busan, Republic of Korea
(4) Bioinformatics Graduate Program, University of California at San Diego School of Medicine, La Jolla, CA, USA

Received: 6 November 2009 Accepted: 8 February 2010 Published online: 5 March 2010

The adrenomedullary hormone epinephrine transduces environmental stressors into cardiovascular events (tachycardia and hypertension). Although the epinephrine biosynthetic enzyme PNMT genetic locus displays both linkage and association to such traits, genetic variation underlying these quantitative phenotypes is not established. Using an integrated suite of computational and experimental approaches, we elucidate a functional mechanism for common (minor allele frequencies > 30%) genetic variants at PNMT. Transcription factor binding motif prediction on mammalian PNMT promoter alignments identified two variant regulatory motifs, SP1 and EGR1, disrupted by G-367A (rs3764351), and SOX17 motif created by G-161A (rs876493). Electrophoretic mobility shifts of approximately 30-bp oligonucleotides containing ancestral versus variant alleles validated the computational hypothesis. Queried against chromaffin cell nuclear protein extracts, only the G-367 and -161A alleles shifted. Specific antibodies applied in electrophoretic gel shift experiments confirmed binding of SP1 and EGR1 to G-367 and SOX17 to -161A. The in vitro allele-specific binding was verified in cella through promoter reporter assays: lower activity for -367A haplotypes cotransfected by SP1 (p = 0.002) and EGR1 (p = 0.034); and enhanced inhibition of -161A haplotypes (p = 0.0003) cotransfected with SP1 + SOX17. Finally, we probed cis/trans regulation with endogenous factors by chromatin immunoprecipitation using SP1/EGR1/SOX17 antibodies. We describe the systematic application of complementary computational and experimental techniques to detect and document functional genetic variation in a trait-associated regulatory region. The results provide insight into cis and trans transcriptional mechanisms whereby common variation at PNMT can give rise to quantitative changes in human physiological and disease traits. Thus, PNMT variants in cis may interact with nuclear factors in trans to govern adrenergic activity.

Thursday, February 25, 2010

Single molecule sequencing

The days of PCR are counted.

Thursday, August 27, 2009

Viewing SOLiD results in the UCSC browser

I'm just getting started figuring out how to do this. The sources of information I'm looking at are the UCSC information for custom tracks and the GTF file format.