zINACTIVE - UTHealth Human Genetics Center Laboratory

About Us

The Human Genetics Center (HGC) was established as a research center within the School of Public Health in September of 1994 at the University of Texas Health Science Center at Houston (UTHealth). It represents the consolidation of two long-standing research Centers that have been joint enterprises of the Graduate School of Biomedical Sciences and the School of Public Health. The HGC Laboratory utilizes the latest genomic technology to understand the etiology of many common chronic diseases in human populations and uses contemporary scientific methods to facilitate the progress of future genomic research which includes elucidation of the interactions between genes and environment and translation of these findings into precision medicine initiatives to help guide decisions regarding the prevention, diagnosis, and treatment of disease. (Photo above by Nash Baker.)

What We Do

The HGC Laboratory serves as the NHLBI-contract facility for the ARIC study and is collaborating with other studies, such as the Framingham Heart Study (FHS), Hispanic Community Health Study / Study of Latinos (HCHS/SOL), National Longitudinal Study of Adolescent to Adult Health (Add Health), and Alzheimer’s Disease Sequencing Project with the aim of understanding or identifying a novel, modifiable molecular basis for disease risk. The CORE also participates in multi-institutional collaborations such as the CHARGE Epigenetics Working Group and meets monthly with Illumina to stay abreast of technical and analytical improvements in working with genome-wide methylation data. We also have the experience and capabilities to analyze multiple tissue types, such as FFPE DNA or fragmented DNA.

Our Expertise

The HGC Core Laboratory has more than two decades of experience and we have extensive knowledge of low and high-throughput genotyping technologies, including Illumina Infinium arrays, Life Technologies TaqMan and Open Array, Agena Biosciences iPlex MassARRAY) and EpiTYPER, and Pyrosequencing genotyping platforms. The HGC Laboratory is fully automated and utilizes a suite of robotic liquid handlers, including the Tecan EVO, Hamilton Starlet, and several Beckman robotic workstations. The HGC Core Laboratory has processed hundreds of thousands of samples to date using Illumina Infinium chemistry from both gDNA and samples derived from formalin-fixed, paraffin-embedded (FFPE) tissue which have resulted in publications in top-tier journals (see references below); including a large Epigenome Wide Association Study of African Americans (Demerath et al., 2015) and a large genetic array project which comprised >62,000 samples (Grove et al., 2013). The HGC Core Laboratory serves as the NHLBI-contract facility for the Atherosclerosis Risk in Communities (ARIC) study, Trans-Omics for Precision Medicine (TOPMed) Centralized Omic REsource (CORE), and is collaborating with other cohorts, such as the Framingham Heart Study (FHS), Cardiac Arrest Blood Study (CABS), Genetic Epidemiology Network of Arteriopathy (GENOA) study, Coronary Artery Risk Development in Young Adults Study (CARDIA), and pediatric leukemia cancer survivors with the aim of understanding or identifying a novel, modifiable molecular basis for disease risk. The Core also participates in multi-institutional collaborations such as the Cohorts for Health and Aging Research in Genomic Epidemiology (CHARGE) Epigenetics working group to stay abreast of technical and analytical improvements in working with genome-wide genetic and methylation data and can perform follow-up measurements or validation of significantly associated CpG sites using EpiTYPER (Agena Bioscience; San Diego, CA).

Data Management

The HGC Laboratory has developed and uses an in-house Laboratory Information Management System (LIMS) for accurate sample tracking and data collection. Data transfer is accomplished using a client-server computing system that integrates specialized laboratory instrumentation, custom client applications, barcode scanning devices, and high-capacity database server technology. Sample inventory and freezer storage are managed using in-house custom applications that track sample attributes, monitor laboratory activities, and store inventory data in SQL Server databases. All samples and reagents are bar-coded, and each piece of equipment has bar-code readers. Data is backed-up nightly and tape backups are stored off-site for safe-keeping.

Overview of Services

Illumina Genotyping and Epigenetics

Whole Genome and Consortium Arrays

Whole-genome genotyping provides an overview of the entire genome, enabling genome-wide discoveries and associations. The following arrays are routinely used, but there are many Illumina arrays not listed which can be easily performed.

Methylation Analysis

  • Methylation EPIC Array
    • MethylationEPIC BeadChip offers a unique combination of comprehensive, expert-selected coverage, including 99% of RefSeq genes, 95% of CpG islands, ENCODE enhancer regions, and other content categories selected by methylation experts, making it ideal for epigenome-wide association studies (EWAS).
  • EpiTYPER DNA Methylation
    • Agena Bioscience’s EpiTYPER DNA methylation analysis technology allows you to interrogate tens to hundreds of CpGs in amplicons of up to 600 bp and detect down to 5% differences in methylation.

Genomic Data Analysis and Quality Control

Genotyping laboratory best practices will be followed using established Illumina protocols (www.illumina.com) and as previously described in Grove et al. It has been well documented that the GenCall algorithm used by Illumina’s GenomeStudio software has difficulty accurately detecting and assigning genotype calls of rare variants (MAF < 0.01) (Korn et al., 2008; Ritchie et al., 2011). To capture these missed rare variants, we will perform additional post-processing steps which include using zCall v3.4_GenomeStudio (Goldstein et al., 2012) to statistically determine genotypes of missing calls. The original dataset from GenomeStudio (with missing calls) will then be compared to the zCalled dataset, and a list of variants in which the heterozygote count is different between the two datasets will be manually reviewed for accuracy and calling. The final dataset will then be converted to PLINK (Purcell et al., 2007) and returned to the provider in an analysis-ready format.

***Please inquire to set up a consultation to discuss your project needs.

Quant Studio Typing

  • Life Technologies TaqMan Allelic Discrimination Assays
    • Applied Biosystems (AB) TaqMan Assay provides a fast and simple way to get single nucleotide polymorphism (SNP) genotyping results. Each TaqMan SNP Genotyping Assay includes two allele-specific TaqMan probes containing distinct fluorescent dyes and a PCR primer pair to detect specific SNP targets.
  • QPCR

Sample Handling and Biobanking Services

  • DNA extraction
    • Gentra Puregene Blood Kits enable the purification of high-molecular-weight (100–200 kb) DNA suitable for archiving. The scalable purification procedure gently removes contaminants and inhibitors and allows large-volume samples to be purified for use as long-term references. Gentra Puregene Blood Kits use approximately 1.5 mL of starting material (buffy coats, saliva, serum, and umbilical cord blood) and yield roughly 200-400 µg of gDNA, but can be scaled to individual project needs.
  • RNA extraction
    • The RNA isolation from PAXgene blood samples is conducted with the MagMAX for Stabilized Blood Tubes RNA Isolation Kit provided by Life Technologies. This kit is ideal for PCR, RT-PCR, and RNA sequencing applications. The kit uses magnetic-based purification components to isolate RNA and yields are routinely ≥3 μg from 2.5 mL of human whole blood.
  • FFPE Repair
    • Formalin-Fixed, Paraffin-Embedded (FFPE)-derived DNA can be used by first repairing degraded DNA using the Infinium HD FFPE DNA Restore Kit from Illumina.
  • Bisulfite Conversion
    • The EZ-96 DNA Methylation™ Kit from Zymo Research is used to convert cytosine to uracil before methylation array analyses. This is the required kit recommended by Illumina for use with their arrays.
  • GLOBINclear™
    • Human Kits are used to deplete >95% of the alpha and beta globin mRNA from total RNA preparations derived from whole blood for samples that will undergo future sequencing. Globin removal allows for the detection of up to 50% more genes and achieves a greater representation of the genome.

Biorepository Facilities:

Long-term liquid nitrogen and ultra-low freezer storage facilities are available for safe storage of biological specimens. All freezers are connected to a call-down alarm system and personnel are available at all times to respond to emergencies.

Leadership

Dr. Eric Boerwinkle is Dean of the School of Public Health and Director of the Human Genetics Center Laboratory which has more than 20 years of experience in large collaborative epidemiological studies involving the determination of human genetic variation. The HGC Laboratory has all the necessary equipment needed to carry out current methodologies in molecular genetics research and is experienced in many methods for genotyping and epityping spanning low to high throughput capacities that can be tailored to meet your individual project goals. DNA and RNA extraction, aliquoting, and management of hundreds of thousands of samples from several large population-based projects are routinely performed.

Dr. Alanna Morrison is Director of the Human Genetics Center and tenured Professor and Chair of the Department of Epidemiology, Human Genetics, and Environmental Sciences at The University of Texas School of Public Health. She is trained in statistical genetics and has expertise in genomic studies of various disease endpoints. Dr. Morrison has carried out several large-scale genomic studies, including genome-wide association studies (GWAS) and evaluation of population-based re-sequencing data. She has led the analysis of genomic data, including association studies involving HapMap and 1000 Genomes imputed variation, exome sequence, Illumina HumanExome v1.0 BeadChip (“exome chip”) array data, and whole genome sequence.

Megan L. Grove is an Associate Director of the Human Genetics Center Laboratory and a Faculty Associate of the Department of Epidemiology, Human Genetics, and Environmental Sciences at The University of Texas School of Public Health. She has managed and supervised daily laboratory operations for over 25 years with a focus on the efficiency and accuracy of high-throughput laboratory technologies that are used to identify genetic and epigenetic variation. She is knowledgeable in multiple molecular genetic laboratory techniques; including DNA isolation, RNA isolation, sample handling and tracking with a custom-designed Laboratory Information Management System (LIMS), and many genotyping and methylation methodologies (e.g., Illumina Infinium, Applied Biosystems TaqMan, and Agena Bioscience MassARRAY and EpiTYPER). She also has extensive experience with collaborative projects and works with several large epidemiologic studies and consortia, including the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, the Trans-Omics for Precision Medicine (TOPMed) Program, the Centers for Common Disease Genomics (CCDG) Consortium, as well as many others.

Location and Hours of Operation

UTHealth Human Genetics Center Laboratory

1200 Pressler Street

RAS E453

Houston TX 77030

713-500-9800

8:00 a.m. - 5:00 p.m. (CT)

 

Contacts

Name Role Phone Email Location
Megan Grove, MS
Faculty Associate
 
713-500-9833
 
HGC_Lab@uth.tmc.edu
 

 
Claudette Huitt
Program Manager
 
713-500-9838
 
HGC_Lab@uth.tmc.edu
 

 

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