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Disease-Specific Projects

See the latest results for some of these projects on our ASHG Meeting page.

Atopic Dermatitis


Lynda Schneider, MD (Principal Investigator)
Ingrid A. Holm, MD, MPH
Louis M. Kunkel, PhD
Isaac Kohane, MD, PhD 

Atopic dermatitis (AD), a type of eczema, is the most common chronic skin disorder of childhood, estimated to affect more than 10 percent of children worldwide. Its incidence is increasing, and most children with AD develop other atopic diseases including food allergy, allergic rhinitis and asthma. This project is phenotyping patients with AD, identifying variants in known and novel genes that may be associated with AD and investigating genetic and environmental risk factors, as well as gene-environment interactions. Currently Boston Children’s Hospital is following approximately 12,000 children with AD. More information on the atopic dermatitis project on

Autism Spectrum Disorder


Louis M. Kunkel, PhD (Principal Investigator)
Christopher Walsh, MD, PhD (Principal Investigator)
Leonard Rappaport, MD
Ingrid A. Holm, MD, MPH
Isaac Kohane, MD, PHD

Autism spectrum disorder (ASD), manifested by severe social, language and cognitive impairments, encompasses a spectrum of genetically related disorders including autism, Pervasive Developmental Disorder–Not Otherwise Specified (PDD-NOS) and Asperger's Disorder. Although heritability estimates exceed 90 percent, a clear genetic cause for ASD has been elusive. This study is conducting behavioral and physical phenotyping of children with ASD and their families, seeking to subdivide this disorder into more homogeneous groups that will increase our power to detect the associated genes and gene pathways.

To do this, we are investigating differences in gene expression in patients’ white blood cells, as well as investigating rare, recessive forms of autism. Our approaches include transmission disequilibrium testing (TDT), affected sib pair (ASP) analysis, genomic sequencing, RNA expression studies and novel Bayesian algorithms (which utilize all data both from phenotypic analysis and from expression arrays).

These studies could lead to a biologically based diagnosis of ASD, a better understanding of the disease process and possible novel interventions. The gene expression research has led to a blood test for autism that is now in clinical development.

Congenital Myopathies


Alan H. Beggs, PhD

The congenital myopathies are rare genetic conditions that cause muscle weakness, sometimes life-threatening. Some children have symptoms at birth, while others develop weakness in childhood or adulthood that impairs walking, breathing and feeding. With the goal of eventually developing effective therapies, this project seeks to better understand the genes and proteins involved in the congenital myopathies by identifying new candidate genes, screening affected patients, developing phenotype/genotype correlations, and exploring gene and protein expression in affected muscle. Expression analysis methods include microarray analysis and functional studies. Our focus includes centronuclear/myotubular myopathy, congenital fiber type disproportion, multiminicore myopathy, nemaline myopathy, and other congenital myopathies as yet undefined. Once we identify a gene, we can model its effects in zebrafish and screen potential drugs.

For more information, visit the Beggs Lab and read coverage on our science blog, Vector:

Developmental Disorders of the Brain 


Christopher A. Walsh, MD, PhD

The Walsh Lab is working to uncover the fundamental cellular and genetic mechanisms directing the development of the cerebral cortex, the largest structure of the human brain. Genetic mutations can alter specific steps of brain development and lead to abnormal brain structure or function, resulting from atypical cell growth, accumulation of cells in abnormal locations in the brain and/or defects in cell function.

Conditions we are interested in include microcephaly, lissencephaly, polymicrogyria and heterotopia, which can be visualized by magnetic resonance imaging (MRI) of the brain and can cause epilepsy, intellectual disability and/or autism. By studying people affected with these conditions and identifying the associated genes and their mutations, we are learning more about the proteins that are important for brain development. It is hoped that this will lead to better diagnostic, care and treatment options for affected children and their families.

For more information, visit the Walsh Lab and read coverage on our science blog, Vector:

Developmental Dysplasia of the Hip (DDH)


Ingrid A. Holm, MD, MPH (Principal Investigator)
Louis M. Kunkel, PhD Young-Jo Kim, MD, PhD
Young-Jo Kim, MD, PhD

Developmental dysplasia of the hip (DDH), often called congenital hip dislocation, is a common disease of early childhood. Its incidence is thought to vary from 1 to 4 per 1,000 births, although an incidence of up to 13 per 1,000 births has been reported. DDH has a strong genetic component, with a polygenic (multiple-gene) component thought to be responsible for acetabular dysplasia, and a single-gene component for the lax joint capsule. Evidence suggests a relatively high rate of generalized joint laxity (GJL) in patients with DDH associated with defects in collagen.

We hypothesize that the association between DDH and collagen genes is strongest in children with GJL, and that we will be able to identify genes associated with DDH in these children. We also hypothesize that patients with GJL inherit DDH in a pattern that is close to Mendelian, whereas those without GJL will show a multifactorial inheritance pattern. We are using transmission disequilibrium testing (TDT) to test the association between DDH and candidate collagen genes and explore the mode of inheritance of DDH in both patients with and without GJL. We will also compare the degree of association of DDH with the candidate genes.

Interstitial Cystitis/Painful Bladder Syndrome


Louis M. Kunkel, PhD (Principal Investigator)
Ingrid A. Holm, MD, MPH

Interstitial cystitis (IC) is a chronic, debilitating syndrome causing urinary urgency, urinary frequency, and/or pelvic pain in the absence of any known cause. Although epithelial dysfunction, abnormal mast cell activity, and nerve damage have all been implicated in IC, the importance of each of these factors is still unclear.

Our preliminary data, from endogamous families in Bulgaria (meaning those that tend to marry within a specific ethnic/social group), indicate that there is linkage between IC and DNA polymorphic markers. By examining the extent of DNA shared on disease chromosomes in this unique cohort, we can identify a set of mutations that will provide tools for the effective diagnosis and treatment of IC.

The aims of this study are to: 1) collect DNA samples and medical/family history data from multigenerational families from the United States and Bulgaria; 2) perform high-density linkage analysis in the most informative pedigrees to establish genetic linkage between IC and DNA polymorphic markers; and 3) identify and verify any positional candidate genes by direct sequencing.

Visit the Kunkel Lab for more information.

Muscular Dystrophy

The muscular dystrophies are a group of diseases that can begin early or later in life, and can be relatively mild, moderate or severe. Severe cases may lead to death in early infancy, and even milder cases can cause significant life-long muscle weakness. Muscular dystrophies are inherited in different ways, including both X-linked and autosomal inheritance.

Since the dystrophin gene was cloned, muscular dystrophy research has significantly progressed. The functions of dystrophin and its associated protein complex (DAPC) are being elucidated. New advances have created the potential for several therapies, and our research is exploring these further with the goal of improving patients’ health and quality of life. For more information, visit Dr. Kunkel’s Neuromuscular Disorders Lab.

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