
Research Summary:
Genetic analysis of complex traits, DNA technology development Summary: We are developing efficient methods to analyze single DNA molecules and applying molecular genetic tools to identify genetic factors associated with complex human traits such as longevity, sudden cardiac arrest, stroke, psoriasis, lupus, and kidney transplantation outcome. We are also conducting studies to identify genetic factors associated with drug response. The overall goal of our research is to develop the tools for genetic analysis of whole genomes and apply these tools to elucidate the genetic factors associated with common human diseases and phenotypes. The sequencing of the human genome and the mapping of common genetic variation by the International HapMap Consortium, in which our lab participated, have inspired an explosion of new technologies, accelerating identification of genetic susceptibility loci. Our phenotypes of interest include kidney transplantation outcomes, longevity, pharmacogenetics of membrane transporters, sudden cardiac death, psoriasis, skin cancer and brian vascular malformations and hemorrhage.
Publications
Clinical impact of pharmacogenetic risk variants in a large chinese cohort.
Identification of De Novo Chromosomal Translocations Disrupting NIPBL in a Patient With Cornelia de Lange Syndrome by Full Genome Analysis.
Optical genome mapping with whole genome sequencing identifies complex chromosomal structural variations in acute leukemia.
Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants.
Polygenic height prediction for the Han Chinese in Taiwan.
A de novo int22h-1/int22h-2-flanked Xq28 deletion-associated preferential X-inactivation in a female with severe hemophilia B.
Highly efficient capture approach for the identification of diverse inherited retinal disorders.
Genetic ancestry and diagnostic yield of exome sequencing in a diverse population.
Author Correction: Diagnostic yield of pediatric and prenatal exome sequencing in a diverse population.
Whole genomic analysis reveals atypical non-homologous off-target large structural variants induced by CRISPR-Cas9-mediated genome editing.
Identification of an 85-kb Heterozygous 4p Microdeletion With Full Genome Analysis in Autosomal Dominant Charcot-Marie-Tooth Disease.
South Asian medical cohorts reveal strong founder effects and high rates of homozygosity.
Diagnostic yield of pediatric and prenatal exome sequencing in a diverse population.
Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry.
High level of complexity and global diversity of the 3q29 locus revealed by optical mapping and long-read sequencing.
Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia.
Publisher Correction: Application of full-genome analysis to diagnose rare monogenic disorders.
Application of full-genome analysis to diagnose rare monogenic disorders.
Correction: Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.
Genome-wide association study of early-onset bipolar I disorder in the Han Taiwanese population.
Genomic Variation and Recent Population Histories of Spotted (Strix occidentalis) and Barred (Strix varia) Owls.
Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome.
Genetic profiles of 103,106 individuals in the Taiwan Biobank provide insights into the health and history of Han Chinese.
Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.
Accurate assembly of the olive baboon (Papio anubis) genome using long-read and Hi-C data.
Towards a reference genome that captures global genetic diversity.
Mutations in Metabotropic Glutamate Receptor 1 Contribute to Natural Short Sleep Trait.
Analysis of putative cis-regulatory elements regulating blood pressure variation.
Genomic Analysis of Historical Cases with Positive Newborn Screens for Short-Chain Acyl-CoA Dehydrogenase Deficiency Shows That a Validated Second-Tier Biochemical Test Can Replace Future Sequencing.
Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation.
Three patients with homozygous familial hypercholesterolemia: Genomic sequencing and kindred analysis.
Targeted Genomic Profiling of Acral Melanoma.
The 22q11 low copy repeats are characterized by unprecedented size and structural variability.
Genome of the Komodo dragon reveals adaptations in the cardiovascular and chemosensory systems of monitor lizards.
Multi-platform discovery of haplotype-resolved structural variation in human genomes.
Genome maps across 26 human populations reveal population-specific patterns of structural variation.
A comprehensive evaluation of the genetic architecture of sudden cardiac arrest.
Integrative approach identifies corticosteroid response variant in diverse populations with asthma.
The Clinical Sequencing Evidence-Generating Research Consortium: Integrating Genomic Sequencing in Diverse and Medically Underserved Populations.
De novo human genome assemblies reveal spectrum of alternative haplotypes in diverse populations.
Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma.
Whole exome and whole genome sequencing with dried blood spot DNA without whole genome amplification.
Pierpont syndrome associated with the p.Tyr446Cys missense mutation in TBL1XR1.
A recurrent, non-penetrant sequence variant, p.Arg266Cys in Growth/Differentiation Factor 3 (GDF3) in a female with unilateral anophthalmia and skeletal anomalies.
High-throughput single-molecule mapping links subtelomeric variants and long-range haplotypes with specific telomeres.
OMBlast: alignment tool for optical mapping using a seed-and-extend approach.
Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer.
Bundle Branch Re-Entrant Ventricular Tachycardia: Novel Genetic Mechanisms in a Life-Threatening Arrhythmia.
Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.
Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation.
Two missense mutations in SALL4 in a patient with microphthalmia, coloboma, and optic nerve hypoplasia.
Atrial Fibrillation Associated Genetic Variants and Left Atrial Histology: Evaluation for Molecular Sub-Phenotypes.
Brief Report: Whole-Exome Sequencing for Identification of Potential Causal Variants for Diffuse Cutaneous Systemic Sclerosis.
In the Wrong Place with the Wrong SNP: The Association Between Stressful Neighborhoods and Cardiac Arrest Within Beta-2-adrenergic Receptor Variants.
Genetic analysis of consanguineous families presenting with congenital ocular defects.
Circulating n-3 fatty acids and trans-fatty acids, PLA2G2A gene variation and sudden cardiac arrest.
Arrhythmogenic Right Ventricular Cardiomyopathy Caused by a Novel Frameshift Mutation.
Genomewide Association Study of Tacrolimus Concentrations in African American Kidney Transplant Recipients Identifies Multiple CYP3A5 Alleles.
Mitochondrial DNA Heteroplasmy Associations With Neurosensory and Mobility Function in Elderly Adults.
Cohort Profile: The Jerusalem Perinatal Family Follow-Up Study.
Endothelin signaling activates Mef2c expression in the neural crest through a MEF2C-dependent positive-feedback transcriptional pathway.
Assembly and diploid architecture of an individual human genome via single-molecule technologies.
A large multiethnic genome-wide association study of prostate cancer identifies novel risk variants and substantial ethnic differences.
DLX4 is associated with orofacial clefting and abnormal jaw development.
COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis.
The genetics of splicing in neuroblastoma.
Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects.
Targeted deep sequencing reveals no definitive evidence for somatic mosaicism in atrial fibrillation.
Effects of the absence of apolipoprotein e on lipoproteins, neurocognitive function, and retinal function.
Prioritizing genes for X-linked diseases using population exome data.
Organic cation transporter variation and response to smoking cessation therapies.
A polymorphism in TLR2 is associated with arterial thrombosis in a multiethnic population of patients with systemic lupus erythematosus.
Novel mutations in PXDN cause microphthalmia and anterior segment dysgenesis.
Application of next generation sequencing to CEPH cell lines to discover variants associated with FDA approved chemotherapeutics.
Finished sequence and assembly of the DUF1220-rich 1q21 region using a haploid human genome.
Who are the Okinawans? Ancestry, genome diversity, and implications for the genetic study of human longevity from a geographically isolated population.
Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups.
Common variation in fatty acid metabolic genes and risk of incident sudden cardiac arrest.
Associations of maternal pre-pregnancy and gestational body size with offspring longitudinal change in BMI.
[NiTiBOND an optimized self-crimping stapes prosthesis for treatment of otosclerosis].
A rare WNT1 missense variant overrepresented in ASD leads to increased Wnt signal pathway activation.
OATP1B1-related drug-drug and drug-gene interactions as potential risk factors for cerivastatin-induced rhabdomyolysis.
HGV2012: leveraging next-generation technology and large datasets to advance disease research.
Nicotinic acetylcholine receptor variation and response to smoking cessation therapies.
Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1.
A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations.
Copy number variation analysis in 98 individuals with PHACE syndrome.
Beta-adrenergic receptor polymorphisms and cardiac graft function in potential organ donors.
Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly.
Common variation in fatty acid genes and resuscitation from sudden cardiac arrest.
Mitochondrial DNA sequence variation is associated with free-living activity energy expenditure in the elderly.
A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel.
Association analysis identifies ZNF750 regulatory variants in psoriasis.
Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma.
A common 5'-UTR variant in MATE2-K is associated with poor response to metformin.
Temporal dissection of tumorigenesis in primary cancers.
GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease.
Cerivastatin, genetic variants, and the risk of rhabdomyolysis.
Replication and extension of association between common genetic variants in SIM1 and human adiposity.
Manitoba-oculo-tricho-anal (MOTA) syndrome is caused by mutations in FREM1.
Functional characterization of liver enhancers that regulate drug-associated transporters.
Sequencing of TNFAIP3 and association of variants with multiple autoimmune diseases.
Angiopoietin-like 4 (ANGPTL4) gene polymorphisms and risk of brain arteriovenous malformations.
Common variants in P2RY11 are associated with narcolepsy.
Meta-analysis confirms the LCE3C_LCE3B deletion as a risk factor for psoriasis in several ethnic groups and finds interaction with HLA-Cw6.
Cerivastatin in vitro metabolism by CYP2C8 variants found in patients experiencing rhabdomyolysis.
Carriers of rare missense variants in IFIH1 are protected from psoriasis.
The DNA damage-binding protein XPC is a frequent target for inactivation in squamous cell carcinomas.
Glucocorticoid receptor gene, low-grade inflammation, and heart failure: the Heart and Soul study.
Cloning mice and men: prohibiting the use of iPS cells for human reproductive cloning.
Reduced expression of integrin alphavbeta8 is associated with brain arteriovenous malformation pathogenesis.
Green technologies for room temperature nucleic acid storage.
Identification and characterization of novel polymorphisms in the basal promoter of the human transporter, MATE1.
Glucocorticoid receptor gene and depression in patients with coronary heart disease: the Heart and Soul Study-2009 Curt Richter Award Winner.
Human subjects are protected from mast cell tryptase deficiency despite frequent inheritance of loss-of-function mutations.
Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease.
Is altered expression of hepatic insulin-related genes in growth hormone receptor knockout mice due to GH resistance or a difference in biological life spans?
EPHB4 gene polymorphisms and risk of intracranial hemorrhage in patients with brain arteriovenous malformations.
Admixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease.
Genomic variation in a global village: report of the 10th annual Human Genome Variation Meeting 2008.
Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity.
Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults.
Importing human pluripotent stem cell lines derived at another institution: tailoring review to ethical concerns.
Genetic variants in multidrug and toxic compound extrusion-1, hMATE1, alter transport function.
Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis.
Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.
Functional genetic variation in the basal promoter of the organic cation/carnitine transporters OCTN1 (SLC22A4) and OCTN2 (SLC22A5).
Identification and characterization of proximal promoter polymorphisms in the human concentrative nucleoside transporter 2 (SLC28A2).
Common variants in interleukin-1-Beta gene are associated with intracranial hemorrhage and susceptibility to brain arteriovenous malformation.
Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype-phenotype relationships.
Further genetic evidence for three psoriasis-risk genes: ADAM33, CDKAL1, and PTPN22.
Population stratification in a case-control study of brain arteriovenous malformation in Latinos.
Differences in allergic sensitization by self-reported race and genetic ancestry.
Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus.
An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients.
A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci.
The Template-Directed Dye-Incorporation Assay with Fluorescence Polarization Detection (FP-TDI).
Common variants in the CRP gene in relation to longevity and cause-specific mortality in older adults: the Cardiovascular Health Study.
Apolipoprotein E e4 allele increases the risk of early postoperative delirium in older patients undergoing noncardiac surgery.
Determination of haplotypes from single DNA molecules: a method for single-molecule barcoding.
Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation.
Identification of NR1I2 genetic variation using resequencing.
Arteriovenous malformation.
Recommendations of the 2006 Human Variome Project meeting.
Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels.
Human Genome Variation 2006: emerging views on structural variation and large-scale SNP analysis.
Rapid DNA mapping by fluorescent single molecule detection.
Heat-inducible translationally controlled tumor protein of Trichinella pseudospiralis: cloning and regulation of gene expression.
African ancestry, socioeconomic status, and kidney function in elderly African Americans: a genetic admixture analysis.
Human Variome Project: an international collaboration to catalogue human genetic variation.
A simple DNA stretching method for fluorescence imaging of single DNA molecules.
Apolipoprotein E epsilon 2 is associated with new hemorrhage risk in brain arteriovenous malformations.
Interleukin-6 involvement in brain arteriovenous malformations.
Polymorphism discovery in 51 chemotherapy pathway genes.
Localization of PSORS1 to a haplotype block harboring HLA-C and distinct from corneodesmosin and HCR.
Lack of support for the association between GAD2 polymorphisms and severe human obesity.
Genetic admixture and asthma-related phenotypes in Mexican American and Puerto Rican asthmatics.
Extract signal out of noise.
Population structure, admixture, and aging-related phenotypes in African American adults: the Cardiovascular Health Study.
Kinetic fluorescence-quenching detection assay for allele frequency estimation.
Single-molecule analysis for molecular haplotyping.
High-throughput genotyping with primer extension fluorescent polarization detection.
A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis.
Identification of a frequent variant in ALG6, the cause of Congenital Disorder of Glycosylation-Ic.
ADAM33 is not associated with asthma in Puerto Rican or Mexican populations.
DNA analysis by fluorescence quenching detection.
Detection of single nucleotide polymorphisms.
Efficient high-throughput resequencing of genomic DNA.
Homogeneous primer extension assay with fluorescence polarization detection.
SNP discovery by direct DNA sequencing.
SNP genotyping and molecular haplotyping of DNA pools.
Sequence variations in the public human genome data reflect a bottlenecked population history.
Novel immunoglobulin superfamily gene cluster, mapping to a region of human chromosome 17q25, linked to psoriasis susceptibility.
Making 'random amplification' predictable in whole genome analysis.
SNP genotyping with fluorescence polarization detection.
Genomics. Genetic association by whole-genome analysis?
Genotyping single-nucleotide polymorphisms by the invader assay with dual-color fluorescence polarization detection.
Advances in molecular medicine.
Genotyping by ligation assays.
The optimal measure of allelic association.
3rd International Meeting on Single Nucleotide Polymorphism and Complex Genome Analysis: SNPs: 'some notable progress'.
Allelic association with SNPs: metrics, populations, and the linkage disequilibrium map.
Fluorescence polarization in homogeneous nucleic acid analysis II: 5'-nuclease assay.
A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms.
Methods for genotyping single nucleotide polymorphisms.
Reflections on a DNA mutation scanning tool.
Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28.
Approaches to allele frequency determination.
Finding a needle in a haystack: detection and quantification of rare mutant alleles are coming of age.
Linkage of a gene for familial hypobetalipoproteinemia to chromosome 3p21.1-22.
Alternative splicing for the alpha1 subunit of soluble guanylate cyclase.
High-throughput genotyping assay approaches.
A general approach to single-nucleotide polymorphism discovery.
Single nucleotide polymorphism libraries: why and how are we building them?
ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes.
Cost-effective staining of DNA with SYBR green in preparative agarose gel electrophoresis.
Fluorescence polarization in homogeneous nucleic acid analysis.
Known mutations of apoB account for only a small minority of hypobetalipoproteinemia.
Homogeneous genotyping assays for single nucleotide polymorphisms with fluorescence resonance energy transfer detection.
Genotyping by mass spectrometry takes flight.
Donor splice mutation (665 + 1 G_T) in familial hypobetalipoproteinemia with no detectable apoB truncation.
Peak height pattern in dichloro-rhodamine and energy transfer dye terminator sequencing.
Reading bits of genetic information: methods for single-nucleotide polymorphism analysis.
A homogeneous, ligase-mediated DNA diagnostic test.
Diabetes mellitus in a new kindred with familial hypobetalipoproteinemia and an apolipoprotein B truncation (apoB-55).
Detection of single nucleotide variations.
Single nucleotide polymorphism hunting in cyberspace.
Fluorescence energy transfer detection as a homogeneous DNA diagnostic method.
Template-directed dye-terminator incorporation (TDI) assay: a homogeneous DNA diagnostic method based on fluorescence resonance energy transfer.
AmpliTaq DNA polymerase, FS dye-terminator sequencing: analysis of peak height patterns.
Peak height variations in automated sequencing of PCR products using Taq dye-terminator chemistry.
Comparative analysis of human DNA variations by fluorescence-based sequencing of PCR products.
Measurement of relative cerebral blood volume changes with visual stimulation by 'double-dose' gadopentetate-dimeglumine-enhanced dynamic magnetic resonance imaging.
Swirls, wrinkles and the whole ball of wax (the source of keratin in cerumen).
Persistence of the foramen of Huschke in the adult: an osteological study.
The immunosuppressant FK506 selectively inhibits expression of early T cell activation genes.
The embryonic development of the human paraseptal cartilage.
Spontaneous temporomandibular joint fistula into the external auditory canal.
Bilateral spontaneous temporomandibular joint herniation into the external auditory canal.
The epidermoid formation (Michaels' structure) in the developing middle ear.
Association between prostaglandin E2 and placental abruption.
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