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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.)

 

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 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 lead 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.

 

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 is managed using in-house custom applications that track sample attributes, monitor laboratory activities and store inventory data to 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.

 

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.

 

Genotyping and Epityping Expertise:  The HGC Core Laboratory has more than two decades of experience and we have extensive knowledge with 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 Hearth 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 has the capacity to perform follow up measurements or validation of significantly associated CpG sites using EpiTYPER (Agena Bioscience; San Diego, CA).

 

Overview of Services

Lab

Illumina 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.

  • Global Screening Array
    • ~660,000 fixed markers; up to 50,000 custom marker add-on capacity
  • HumanOmni2.5-8
    • >2.3 million fixed markers; up to 200,000 custom marker add-on capacity
  • Human Omni2.5Exome
    • >2.6 million fixed markers
  • HumanOmniExpress
    • ~710,000 fixed markers; up to 30,000 custom marker add-on capacity
  • Human Exome
    • 243,345 fixed markers; up to 400,000 custom marker add-on capacity
  • HumanCoreExome
    • 551,839 fixed markers; up to 100,000 custom marker add-on capacity
  • MEGAEX  Array (formerly African Diaspora_PowerChip)
    • >1.4 million fixed markers; up to 245,000 custom marker add on capacity
  • MEG Array
    • >1.7 million fixed markers; up to 245,000 custom marker add-on capacity

Custom Mid to High-Plex Genotyping

  • Illumina iSelect Beadchips
    • Design a custom genotyping panel that supports up to 1,000,000 custom markers (SNPs, indels, and CNVs). iSelect can be deployed on either the 24-sample HD (3,072 to 90,000), 24-sample HTS (90,001 to 700,000), or other BeadChip format to support greater than 700,000 markers. Creation of these custom assays enables focused, high-throughput genotyping applications tailored to your unique project needs.

Custom Low to Mid-Plex Genotyping

  • 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.
  • Agena Bioscience MassARRAY
    • 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.

Epigenetics: Methylation Analysis

  • Illumina 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.

 

Illumina Laboratory Best Practices 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 detect and assigning genotype calls of rare variants (MAF < 0.01) (Korn et al., 2008; Ritchie et al., 2011). In order 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 a analysis-ready format.

 

Genomic Data Analysis and Quality Control

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

 

Sample Handling and Storage

 

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.

 

DNA extraction
Gentra Puregene Blood Kits enable 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 the magnetic-based purification components to isolate RNA and yields are routinely ≥3 μg from 2.5 mL of human whole blood.

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 detection of up to 50% more genes and achieves greater representation of the genome.

 

 

References

 

  1. Peloso, G.M., Auer, P.L., Bis, J.C., Voorman, A., Morrison, A.C., Stitziel, N.O., Brody, J.A., Khetarpal, S.A., Crosby, J.R., Fornage, M., et al. (2014). Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks. Am J Hum Genet 94, 223-232.
  2. Wessel, J., Chu, A.Y., Willems, S.M., Wang, S., Yaghootkar, H., Brody, J.A., Dauriz, M., Hivert, M.F., Raghavan, S., Lipovich, L., et al. (2015). Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nature communications 6, 5897.
  3. Lunetta, K.L., Day, F.R., Sulem, P., Ruth, K.S., Tung, J.Y., Hinds, D.A., Esko, T., Elks, C.E., Altmaier, E., He, C., et al. (2015). Rare coding variants and X-linked loci associated with age at menarche. Nature communications 6, 7756.
  4. Huffman, J.E., de Vries, P.S., Morrison, A.C., Sabater-Lleal, M., Kacprowski, T., Auer, P.L., Brody, J.A., Chasman, D.I., Chen, M.H., Guo, X., et al. (2015). Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF. Blood 126, e19-29.
  5. van der Lee, S.J., Holstege, H., Wong, T.H., Jakobsdottir, J., Bis, J.C., Chouraki, V., van Rooij, J.G., Grove, M.L., Smith, A.V., Amin, N., et al. (2015). PLD3 variants in population studies. Nature 520, E2-3.
  6. Aslibekyan, S., Demerath, E.W., Mendelson, M., Zhi, D., Guan, W., Liang, L., Sha, J., Pankow, J.S., Liu, C., Irvin, M.R., et al. (2015). Epigenome-wide study identifies novel methylation loci associated with body mass index and waist circumference. Obesity (Silver Spring) 23, 1493-1501.
  7. Hagg, S., Ganna, A., van der Laan, S.W., Esko, T., Pers, T.H., Locke, A.E., Berndt, S.I., Justice, A.E., Kahali, B., Siemelink, M.A., et al. (2015). Gene-Based Meta-Analysis of Genome-Wide Association Studies Implicates New Loci Involved in Obesity. Hum Mol Genet.
  8. Yu, B., Zheng, Y., Alexander, D., Morrison, A.C., Coresh, J., and Boerwinkle, E. (2014). Genetic determinants influencing human serum metabolome among African Americans. PLoS Genet 10, e1004212.
  9. Franceschini, N., Hu, Y., Reiner, A.P., Buyske, S., Nalls, M., Yanek, L.R., Li, Y., Hindorff, L.A., Cole, S.A., Howard, B.V., et al. (2014). Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: the PAGE study. PLoS One 9, e113203.
  10. Carty, C.L., Bhattacharjee, S., Haessler, J., Cheng, I., Hindorff, L.A., Aroda, V., Carlson, C.S., Hsu, C.N., Wilkens, L., Liu, S., et al. (2014). Analysis of metabolic syndrome components in >15 000 african americans identifies pleiotropic variants: results from the population architecture using genomics and epidemiology study. Circ Cardiovasc Genet 7, 505-513.
  11. Lin, D.Y., Tao, R., Kalsbeek, W.D., Zeng, D., Gonzalez, F., 2nd, Fernandez-Rhodes, L., Graff, M., Koch, G.G., North, K.E., and Heiss, G. (2014). Genetic association analysis under complex survey sampling: the Hispanic Community Health Study/Study of Latinos. Am J Hum Genet 95, 675-688.
  12. Gong, J., Schumacher, F., Lim, U., Hindorff, L.A., Haessler, J., Buyske, S., Carlson, C.S., Rosse, S., Buzkova, P., Fornage, M., et al. (2013). Fine Mapping and Identification of BMI Loci in African Americans. Am J Hum Genet 93, 661-671.
  13. Wu, Y., Waite, L.L., Jackson, A.U., Sheu, W.H., Buyske, S., Absher, D., Arnett, D.K., Boerwinkle, E., Bonnycastle, L.L., Carty, C.L., et al. (2013). Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained. PLoS Genet 9, e1003379.
  14. Scott, R.A., Lagou, V., Welch, R.P., Wheeler, E., Montasser, M.E., Luan, J., Magi, R., Strawbridge, R.J., Rehnberg, E., Gustafsson, S., et al. (2012). Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet 44, 991-1005.
  15. Locke, A.E., Kahali, B., Berndt, S.I., Justice, A.E., Pers, T.H., Day, F.R., Powell, C., Vedantam, S., Buchkovich, M.L., Yang, J., et al. (2015). Genetic studies of body mass index yield new insights for obesity biology. Nature 518, 197-206.
  16. Spencer, K.L., Malinowski, J., Carty, C.L., Franceschini, N., Fernandez-Rhodes, L., Young, A., Cheng, I., Ritchie, M.D., Haiman, C.A., Wilkens, L., et al. (2013). Genetic variation and reproductive timing: African American women from the Population Architecture using Genomics and Epidemiology (PAGE) Study. PLoS One 8, e55258.
  17. Buyske, S., Wu, Y., Carty, C.L., Cheng, I., Assimes, T.L., Dumitrescu, L., Hindorff, L.A., Mitchell, S., Ambite, J.L., Boerwinkle, E., et al. (2012). Evaluation of the metabochip genotyping array in African Americans and implications for fine mapping of GWAS-identified loci: the PAGE study. PLoS One 7, e35651.
  18. Avery, C.L., Sethupathy, P., Buyske, S., He, Q., Lin, D.Y., Arking, D.E., Carty, C.L., Duggan, D., Fesinmeyer, M.D., Hindorff, L.A., et al. (2012). Fine-mapping and initial characterization of QT interval loci in African Americans. PLoS Genet 8, e1002870.
  19. Hiltunen, T.P., Donner, K.M., Sarin, A.P., Saarela, J., Ripatti, S., Chapman, A.B., Gums, J.G., Gong, Y., Cooper-DeHoff, R.M., Frau, F., et al. (2015). Pharmacogenomics of hypertension: a genome-wide, placebo-controlled cross-over study, using four classes of antihypertensive drugs. Journal of the American Heart Association 4, e001521.
  20. Demerath, E.W., Guan, W., Grove, M.L., Aslibekyan, S., Mendelson, M., Zhou, Y.H., Hedman, A.K., Sandling, J.K., Li, L.A., Irvin, M.R., et al. (2015). Epigenome-wide association study (EWAS) of BMI, BMI change and waist circumference in African American adults identifies multiple replicated loci. Hum Mol Genet 24, 4464-4479.
  21. Grove, M.L., Yu, B., Cochran, B.J., Haritunians, T., Bis, J.C., Taylor, K.D., Hansen, M., Borecki, I.B., Cupples, L.A., Fornage, M., et al. (2013). Best practices and joint calling of the HumanExome BeadChip: the CHARGE Consortium. PLoS One 8, e68095.
  22. Korn, J.M., Kuruvilla, F.G., McCarroll, S.A., Wysoker, A., Nemesh, J., Cawley, S., Hubbell, E., Veitch, J., Collins, P.J., Darvishi, K., et al. (2008). Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs. Nat Genet 40, 1253-1260.
  23. Ritchie, M.E., Liu, R., Carvalho, B.S., and Irizarry, R.A. (2011). Comparing genotyping algorithms for Illumina's Infinium whole-genome SNP BeadChips. BMC bioinformatics 12, 68.
  24. Goldstein, J.I., Crenshaw, A., Carey, J., Grant, G., Maguire, J., Fromer, M., O'Dushlaine, C., Moran, J.L., Chambert, K., Stevens, C., et al. (2012). zCall: a rare variant caller for array-based genotyping. Bioinformatics 28, 2543-2545.
  25. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J., et al. (2007). PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81, 559-575.

Leadership

Eric Boerwinkle, PhD, Dean UTHealth School of Public Health; Professor of Epidemiology, Human Genetics and Environmental Sciences 

Alanna C. Morrison, PhD, FAHA, Professor and Department Chair, Department of Epidemiology, Human Genetics and Environmental Sciences; Director, Human Genetics Center

Megan L. Grove, MS, Principal Laboratory Specialist; Associate Director, Human Genetics Center Laboratory

Location and Hours of Operation

UTHealth Human Genetics Center Laboratory

1200 Pressler Street

Houston TX 77030

713-500-9800

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

Contacts

Name Role Phone Email Location
Megan Grove, MS
Principal Laboratory Specialist; Associate Director
 
713-500-9800
 
HGC_lab@uth.tmc.edu
 

 

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