Dobyns Lab

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Dobyns Lab

Pipeline

Our research pipeline is built from several components:

Phenotyping

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Every project in the Dobyns Lab begins with an accurate description (phenotyping) of the brain disorder of interest. This work can include, in varying combinations, close study of:

Brain imaging

The recognition and classification of human brain malformations has long formed the center of phenotyping by the Dobyns Lab. This work has led to the discovery of numerous causative genes for these conditions, and has improved our understanding of how the human brain develops. William B. Dobyns has played a central role in the classification systems of malformations of the forebrain and midbrain-hindbrain, and serves as an international resource on their diagnosis. To have a brain MRI reviewed by Dr. Dobyns, you may contact us here.

Growth parameters

The classification of many human neurodevelopmental disorders often begins with such basic data as growth parameters. Accurate longitudinal head size data can help to differentiate classes of children with microcephaly (small head size) and macrocephaly (large head size). Length and height can also facilitate the recognition of specific syndromes.

Child developmental data

With improved recognition of the spectrum of human neurodevelopmental disorders, the importance of not only depth but also breadth of developmental phenotyping has emerged. To this end, the Dobyns Lab examines traditional child development data, but is also developing novel tools to quantitate wider functional domains such as mood, GI function, sleep, and other areas where abnormalities in neurologic function may be reflected.

Dysmorphology

Numerous genetic syndromes are characterized by specific patterns of dysmorphologic signs. Examination of clinical photographs, and use of standardized terminology aids in the recognition of rare disorders.

Electroencephalogram (EEG) data

The Dobyns Lab studies several pediatric epilepsy disorders, including early infantile epileptic encephalopathy, infantile spasms, and Lennox-Gastaut syndrome. EEG data help to characterize these disorders, and there are numerous unanswered questions about connection between EEG findings and clinical outcome.

Video of movement disorders

Recently pediatric neurologists have become aware that many neurodevelopmental disorders also feature involuntary movements -- many of which were often viewed too simply in the past as "cerebral palsy". In some cases, recognition of these movements can lead to more rapid diagnosis of a syndrome and assist with classification. We use standardized assessments of movement disorders appropriate for pediatric patients.

Gene Discovery

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The Dobyns Lab uses a combination of molecular tools to discover causative genes for human neurodevelopmental disorders:

Genomic Copy Number Analysis

We make use of a variety of chromosomal microarray platforms to detect genomic copy number changes. At times, these data allow us to identify a causative gene within a region affected by copy number. Other times, we may identify areas that contribute to a given phenotype. A variety of methods are used to visualize and verify copy number array results, including fluorescence in situ hybridization and/or quantitative PCR. Results from copy number experiments contribute directly to our bioinformatics pipeline, including the RViewer project.

Sequencing

We use both traditional Sanger sequencing of single candidate genes to discover pathogenic mutations, as well as next-generation sequencing technologies that allow us to examine almost all genes ("the exome") at once. Research subjects for exome sequencing are carefully selected, and our downstream variant analysis is based on our hypotheses about whether a disorder may be autosomal recessive or a sporadic/new dominant condition. We will begin whole genome sequencing projects in the near future. Next-generation sequencing results also contribute to our growing database of variants, as well as other bioinformatics projects.

Bioinformatics

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The Dobyns Lab is involved in a number of bioinformatics projects aimed at organizing and understanding the large amount of genomic data we produce:

Database of NGS Variants

We maintain a growing database of genetic variants identified during next-generation sequencing experiments. This database allows us to more efficiently filter our data, and recognize important patterns that may contribute to neurodevelopmental diseases.

LISDB2

The Dobyns Lab maintains one of the largest repositories of phenotype and genomic data on neurodevelopmental disorders, LISDB2. This database was developed in collaboration with Dr. Natalia Maltsev of the Computation Institute at the University of Chicago. Efforts are underway to federate our dataset with that of other researchers in the field, so that causes of neurodevelopmental disorders may be identified more efficiently. LISDB2 will eventually incorporate phenotype and genotype analysis tools currently under development.

RViewer

While working with copy number variation (CNV) data, we recognized the need for a tool that allowed simultaneous analysis of multiple areas of CNV and linked to the many publicly-available informatics resources already available. We collaborated with Dr. Inna Dubchak of the Genomics Division of the Lawrence Berkeley National Laboratory and the DOE Joint Genome Insitute to develop a tool to allow comparative analysis of multiple CNV areas in parallel. The result is RViewer.