DNA sample being pipetted into petri dish with DNA gel in background

The objective of the Molecular Phenotyping and Genotyping Core is to support Joslin and external investigators in the study of molecular mechanisms of disease by providing equipment, expertise, and services in molecular phenotyping, including nucleic acid sequence analyses, gene expression, and other "-omics" analyses, which would be too specialized or costly for individual laboratories to perform independently.

Formerly known as the Advanced Genomics and Genetics Core, the Molecular Phenotyping Core is newly named in recognition of the expansion of its analytical capacities to reflect not only genetic and genomic analyses but also metabolic phenotyping.

Core Leadership

Alessandro Doria
Alessandro Doria, MD, PhD, MPH
Senior Investigator, Section on Genetics and Epidemiology
Professor of Medicine, Harvard Medical School
Professor in the Department of Epidemiology, Harvard T.H. Chan School of Public Health
Mary Elizabeth Patti
Mary-Elizabeth Patti, MD
Staff Physician
Director, Hypoglycemia Clinic
Co-Director, Molecular Phenotyping Core
Associate Professor of Medicine, Harvard Medical School

Services Provided

The Core provides sizing, quantitation, and quality control services of DNA and RNA samples using the Agilent 2100 Bioanalyzer system. This is often used in preparation for high-throughput sequencing, or other expression analysis.

The Core houses Seahorse XFe96 and XF24 Bioanalyzers. This instrument can be used to analyze cultured cells, tissue explants, and whole blood samples though quantification of oxygen consumption and extracellular acidification (a surrogate for glycemic flux and metabolic flexibility).

Extraction of high-quality DNA from human specimens, including blood samples.

The Core repository currently includes about 6,000 DNA samples organized in eight panels, some of which include special forms of diabetes not available in other collections.

The Covaris E220 Ultrasonicator provides high-quality shearing of 1 to 96 gDNA samples in a single run.

The Biorad QX200 Droplet Digital PCR System is now available! This ddPCR system provides absolute quantification of target DNA or RNA molecules for EvaGreen or probe-based applications in a 96-sample format. Its high precision and sensitivity provides researchers with the following advantages over traditional real-time PCR: 1) Absolute quantification of DNA without the use of a standard curve; 2) Detection of rare DNA mutations and copy number variation; 3) Accurate gene expression analysis of low-abundant coding and non-coding RNAs; 4) Analysis of NGS library quantity and quality without the use of a standard curve. Equipment components include the QX200 Droplet Generator, QX200 Droplet Reader, PX1 PCR Plate Sealer, and C1000 Touch Thermal Cycler.

The Core assists Joslin investigators using DNA repository panels in accessing the corresponding clinical data and exporting them in formats compatible with genetic analysis programs. Additionally, core personnel provides extensive informal assistance with experimental design, choice of array type or sequencing approaches, and troubleshooting for both array and PCR analysis hardware and software issues.

A next-gen sequencing assay has been developed by the Core to simultaneously screen all known monogenic diabetes genes (e.g. MODY, neonatal diabetes) for mutations and to type all known SNPs associated with T1D, T2D, and complications. This assay will allow the standardized collection of genetic data to study the influence of genetic variation on the response to treatments and exposures in interventional and observational studies at a reasonable price.

The core offers full-service library prep and capture for custom designed or whole exome NGS projects, with multiplexing of to 96 samples per capture. The sequencing of prepared libraries is completed by forwarding samples to The Bauer Core Facility (https://bauercore.fas.harvard.edu/). Core personnel is available to assist in custom NGS array design

The Core houses two ABI 7900's (384 well) and one ABI 7000 (96-well).

The Core provides a single nucleotide polymorphism (SNP) typing service based on the Applied Biosystems TaqMan SNP Genotyping Assays. Typically, these are SNPs that have been identified by genome-wide association studies (GWAS) or resequencing projects as being associated with diabetes or its complications, and for which replication is being sought in other studies.

If any of your research has been supported in full or in part by our Core, please acknowledge our NIH/NIDDK grant as follows: "Supported by the Molecular Phenotyping & Genotyping Core of P30 DK036836."

For services related to the Core’s Genetics component, please contact Christine Mendonca at Christine.Mendonca [at] joslin.harvard.edu

For services related to the Core’s Genomics component, please contact Christine Qiong Zhou at Qiong.Zhou [at] joslin.harvard.edu

iLab Application Suite

You can get information on the process for ordering and pricing from Joslin's iLab Services page.